Phenylamino isothiazole carboxamidines as MEK inhibitors

ABSTRACT

The invention concerns compounds which inhibit MEK and which have activity as anti-neoplastic agents. These compounds include N-substituted-3-hydroxy-5-arylamino-isothiazole-4-carboxamidines. Also included are the tautomeric isothiazol-3(2H)-ones.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No. 60/645,425, filed Jan. 20, 2005; U.S. Provisional Application No. 60/653,340, filed Feb. 16, 2005; U.S. Provisional Application No. 60/675,397, filed Apr. 27, 2005; U.S. Provisional Application No. 60/685,131, filed May 26, 2005; U.S. Provisional Application No. 60/685,194, filed May 26, 2005; U.S. Provisional Application No. 60/688,005, filed Jun. 6, 2005; U.S. Provisional Application No. 60/688,006, filed Jun. 6, 2005; U.S. Provisional Application No. 60/688,628, filed Jun. 7, 2005; and U.S. Provisional Application No. 60/691,698, filed Jun. 16, 2005. All of these applications are hereby incorporated herein by reference.

FIELD OF THE INVENTION

The invention concerns compounds which inhibit MEK and which have activity as anti-neoplastic agents. These compounds include N-substituted-3-hydroxy-5-aryl-isothiazole-4-carboxamidines. Also included are the tautomeric isothiazol-3(2H)-ones.

BACKGROUND OF THE INVENTION

Oncogenes—genes that contribute to the production of cancers—are generally mutated forms of certain normal cellular genes (“proto-oncogenes”). Oncogenes often encode abnormal versions of signal pathway components, such as receptor tyrosine kinases, serine-threonine kinases, or downstream signaling molecules. The central downstream signaling molecules are the Ras proteins, which are anchored on the inner surfaces of cytoplasmic membranes, and which hydrolyze bound guanosine triphosphate (GTP) to guanosine diphosphate (GDP). When activated by a growth factor, growth factor receptors initiate a chain of reactions that leads to the activation of guanine nucleotide exchange activity on Ras. Ras alternates between an active “on” state with a bound GTP (hereafter “Ras.GTP”) and an inactive “off” state with a bound GDP. The active “on” state, Ras.GTP, binds to and activates proteins that control the growth and differentiation of cells.

For example, in the “mitogen-activated protein kinase (MAP kinase) cascade,” Ras.GTP leads to the activation of a cascade of serine/threonine kinases. One of several groups of kinases known to require a Ras.GTP for their own activation is the Raf family. The Raf proteins activate “MEK1” and “MEK2,” abbreviations for mitogen-activated ERK-activating kinases (where ERK is extracellular signal-regulated protein kinase, another designation for MAPK). MEK1 and MEK2 are dual-function serine/threonine and tyrosine protein kinases and are also known as MAP kinase kinases. Thus, Ras.GTP activates Raf, which activates MEK1 and MEK2, which activate MAP kinase (MAPK). Activation of MAP kinase by mitogens appears to be essential for proliferation, and constitutive activation of this kinase is sufficient to induce cellular transformation. Blockade of downstream Ras signaling, as by use of a dominant negative Raf-1 protein, can completely inhibit mitogenesis, whether induced from cell surface receptors or from oncogenic Ras mutants.

The interaction of Raf and Ras is a key regulatory step in the control of cell proliferation. To date, no substrates of MEK other than MAPK have been identified; however, recent reports indicate that MEK may also be activated by other upstream signal proteins such as MEK kinase or MEKK1 and PKC. Activated MAPK translocates and accumulates in the nucleus, where it can phosphorylate and activate transcription factors such as Elk-1 and Sap1a, leading to the enhanced expression of genes such as that for c-fos.

Once activated, Raf and other kinases phosphorylate MEK on two neighboring serine residues, S²¹⁸ and S²²² in the case of MEK-1. These phosphorylations are required for activation of MEK as a kinase. In turn, MEK phosphorylates MAP kinase on two residues separated by a single amino acid: a tyrosine, Y¹⁸⁵, and a threonine, T¹⁸³. MEK appears to associate strongly with MAP kinase prior to phosphorylating it, suggesting that phosphorylation of MAP kinase by MEK may require a prior strong interaction between the two proteins. Two factors—MEK's unusual specificity and its requirement for a strong interaction with MAP kinase prior to phosphorylation—suggest that MEK's mechanism of action may differ sufficiently from the mechanisms of other protein kinases as to allow for selective inhibitors of MEK. Possibly, such inhibitors would operate through allosteric mechanisms rather than through the more usual mechanism involving blockage of an ATP binding site.

MEK1 and MEK2 are, therefore, validated and accepted targets for anti-proliferative therapies, even when the oncogenic mutation does not affect MEK structure or expression. See, e.g., U.S. Patent Publications 2003/0149015 by Barrett et al. and 2004/0029898 by Boyle et al.

An N-unsubstituted, 3-hydroxy-5-phenyoxyphenyl-isothiazole-4-carboxyamidine having anti MEK activity was described in a patent publication commonly assigned with the present application. US 2004/0039037 (Feb. 26, 2004). No analogs or derivatives of the compound were described. A group of 3-phenyloxy-5-alkylureido-isothiazole-4-carboxamide kinase inhibitors having anti-proliferative activity was reported in U.S. Pat. No. 6,548,526 and No. 6,235,764. These compounds were not noted to be MEK inhibitors; they inhibited a tyrosine kinase activity associated with the vascular endothelial growth factor receptor (VEGF).

A second group of isothiazole-4-carboxamides with anti-proliferative activity via blockage of Trk tyrosine kinase—not a VEGF-associated kinase—was described in U.S. Patent Publication 2004/0152691. The compounds are 3-arylsulfanyl-5-heteroarylamino-isothiazoles.

Isoxazole inhibitors of MEK-activated kinase (ERK or MAPK) were described in U.S. Pat. No. 6,649,640 and No. 6,495,582. Rather than 3-hydroxy-4-carboxamides or 3-hydroxy-4-carboxamidines, the compounds disclosed in these patents are 3-unsubstituted or 3-amino substituted-4-aryl isoxazoles.

BRIEF DESCRIPTION OF THE INVENTION

In general, this invention provides a compound of formula I

where Ar¹ is phenyl, pyridyl, pyrimidyl, pyridazinyl, or triazinyl, in which all ring carbon atoms are optionally substituted with substituents R₁, R₂, and R₃, where R₁, R₂, and R₃ are selected independently from hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₆ alkyl; O—C₁-C₆ alkyl; C₂-C₆ alkenyl; C₂-C₆ alkynyl; C₃-C₆ cycloalkyl; C₅-C₆ cycloalkenyl, C₅-C₆ cycloalkadienyl, O—C₁-C₆ alkyl, O—C₂-C₆ alkenyl, C₁-C₆ alkyl-C(═O)—, C₁-C₆ alkenyl-C(═O)—, C₁-C₆ alkyl-O—C(═O)—, C₁-C₆ alkenyl-O—C(═O)—, C₁-C₆ alkyl-C(═O)—O—, C₁-C₆ alkenyl-C(═O)—O—, isothiazolyl, isoxazolyl, oxazolyl, oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl, CH₃SO₂—, NH₂SO₂—, CH₃NHSO₂—, CH₃SO₂NH—, R₇R₈N—, R₈R₉NCH₂—, R₇C(═O)NH, —S(O)₂NR₇R₈, or R₇R₈NC(═O), wherein R₇-R₉ are, independently, H, C₁-C₄ alkyl, phenyl, or C₂-C₆ alkenyl; R₁₀—C≡C—, wherein R₁₀ is H, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₃-C₆ cycloalkyl, C₅-C₆ cycloalkenyl, (CH₃)₂NCH₂—, phenyl or (CH₃)₂NCH₂CH₂—; R₄ is H, C₁-C₃ alkyl, or C₁-C₃ alkenyl, said alkyl and said alkenyl groups optionally substituted with, independently, 1, 2, or 3 halogen atoms, O—C₁₋₂ alkyl, C₁-C₃ alkenyl, and N(H)C₁₋₂ alkyl; R₅ is H or C₁-C₃ alkyl; and in which all alkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, and heteroaryl groups in R₁-R₁₀ are optionally substituted with one, two, or three groups selected from F, Cl, Br, I, OH, CN, C₁-C₄ alkyl, C₁-C₄ alkoxyl, and C₂-C₄ alkenyl; or any of the pairs R₁ and R₂, R₇ and R₈, or R₈ and R₉ are attached to adjacent carbons and, together with the ring atoms to which they are attached, form an additional, fused, five- or six-membered ring, optionally containing one or two heteroatoms selected from O, N, and S, which ring may be aromatic or aliphatic; wherein all alkyl, alkenyl, and cycloalkyl groups and all rings are optionally substituted with 1-3 halogen atoms, and all rings are also optionally substituted with 1-3 C₁-C₃ alkyl groups or trifluoromethyl groups; A is O, S, CH₂, N₂, C(O), NHC(O), C(O)CH₂, or CH₂C(O); or Ar¹-A is

where the five-membered ring is fused to Ar¹ and Y is NH, S, or O, or Ar¹-A is

where the dotted line represents an optional double bond, the five-membered ring is fused to Ar¹, and R_(x) is selected from substituents listed above for R₃; or Ar¹-A is

where the five-membered ring is fused to Ar¹, and R_(x) is selected from substituents listed above for R₃; Ar² is phenyl, pyridyl, pyrimidyl, pyridazinyl, or triazinyl, where ring carbon atoms are optionally substituted with substituents R₄-R₆, where R₄ is defined as for R₁-R₃ above; R₅ and R₆ are, independently, H, F, Cl, Br, CH₃, or CF₃; and in which all alkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, and heteroaryl groups in R₁-R₉ are optionally substituted with one, two, or three groups selected from F, Cl, Br, I, OH, CN, C₁-C₄ alkyl, C₁-C₄ alkoxyl, and C₂-C₄ alkenyl; which are selected independently from H, F, Cl, Br, CH₃, or CF₃; or Ar²—NH— is

where R_(y) is selected from substituents listed above for R₃; and R′ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups are optionally substituted with one to three groups selected independently from hydroxy, halogen, and methyl; or R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is a five- or six-membered ring or a 9-14-membered fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds; or R′ is —CH(CH₂OH)CH₂D, where D is selected from imidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, and adamantin-1-yl.

In one generic embodiment, this invention provides a compound of formula I where Ar¹ and Ar² are both 6-membered rings.

In another generic embodiment, this invention provides a compound of formula I in which A is S, CH₂, N₂, CO, C(O)CH₂, or NHC(O).

In another generic embodiment, this invention provides a compound of formula I, in which A is O, C(O), or CH₂C(O).

In another generic embodiment, this invention provides a compound of formula I where R′ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl, said phenyl group or groups optionally substituted with one to three groups selected independently from hydroxy, halogen, and methyl.

In another generic embodiment, this invention provides a compound of formula I where R′ is —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups are optionally substituted with one to three groups selected independently from hydroxy, halogen, and methyl.

In another generic embodiment, this invention provides a compound of formula I where R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is a five- or six-membered ring or a 9-14-membered fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds.

In still another generic embodiment, this invention provides a compound of formula I where R′ is CH(CH₂OH)CH₂D, where D is selected from imidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, and adamantin-1-yl.

In one subgeneric embodiment, this invention provides a compound of formula II

in which A is —O—, —CH₂—, —N₂—, —CH₂C(O)—, C(O)CH₂, —S—, or —C(O)—; R₁, R₂, and R₃ are, independently, hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂; or R₁ and R₂ are attached to adjacent carbons and, together with the ring atoms to which they are attached, form an additional, fused, five- or six-membered ring, optionally containing one heteroatom, which ring may be aromatic or aliphatic; R₄-R₆ are, independently, H, F, Cl, Br, CH₃, or CF₃; R* is H, except when R₁ and R₂ are both F; when R₁ and R₂ are both F, R* is either H or Cl; R′ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups are optionally substituted with one to three groups selected independently from hydroxy, halogen, and methyl; or R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is a five- or six-membered ring or a 9-14-membered fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds; or R′ is —CH(CH₂OH)CH₂D, where D is selected from imidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, and adamantin-1-yl.

In another subgeneric embodiment, this invention provides a compound of formula II in which A is O.

In a more specific embodiment, this invention provides a compound of formula II in which A is O and R′ is —CH(CH₂OH)CH₂D, where D is selected from imidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, and adamantin-1-yl.

In another embodiment, this invention provides a compound of formula II in which A is O and R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is a five- or six-membered ring or a 9-14-membered fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds.

In another embodiment, this invention provides a compound of formula II in which A is O and R′ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups are optionally substituted with one to three groups selected independently from hydroxy, halogen, and methyl.

In another subgeneric embodiment, this invention provides a compound of formula II in which A is —O—, R₁ is 2-C(O)G, where G is selected from:

OJ, where J is isopropyl, cyclopropyl, cyclopentyl, dimethylamino, or methoxyethyl; and

NHJ′ where J′ is methyl, ethyl, isopropyl, cyclopropyl, dimethylaminomethyl, or 3-methyl-2-yl-butanoic acid methyl ester and —N(CH₃)₂; or N-methyl piperazinyl;

R₂ and R₃ are H; and R₄ is isopropyl or 1-hydroxy-isopropyl.

In another embodiment, this invention provides a compound of formula II in which A is O; R′ is —CH(CH₂OH)CH₂D, where D is selected from imidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, and adamantin-1-yl; R₁ is H; R₂ is 2-Cl, 2-Me, 2-CF₃, 3-F, 3-Me, 3-N(CH₃)₂; 3-C(O)OEt, 3-C(O)OMe, 4-Cl, or 4-OH, and R₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈; —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula II in which A is O; R′ is —CH(CH₂OH)CH₂D, where D is selected from imidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, and adamantin-1-yl; R₁ is 2-Me, 2-F, or 2-Cl; R₂ is 3-Me, 3-F, 3-Cl, 5-Me, 5-F, 5-Cl or 3-CF₃; and R₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula II in which A is O; R′ is —CH(CH₂OH)CH₂D, where D is selected from imidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, and adamantin-1-yl; R₁ is 5-Cl; R₂ is —C(O)NR₇R₈, or —S(O)₂NR₇R₈, and R₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula II in which A is O and R′ is (CH₂)_(n)-G; R₁ is H; R₂ is 2-Cl, 2-Me, 2-CF₃, 3-F, 3-Me, 3-N(CH₃)₂; 3-C(O)OEt, 3-C(O)OMe, 4-Cl, or 4-OH; and R₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula II in which A is O and R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is a five- or six-membered ring or a 9- to 14-membered fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds; R₁ is 2-Me, 2-F, or 2-Cl; R₂ is 3-Me, 3-F, 3-Cl, 5-Me, 5-F, 5-Cl or 3-CF₃; and R₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula II in which A is O, R′ is (CH₂)_(n)-G; R₁ is 5-Cl; R₂ is —C(O)NR₇R₈, or —S(O)₂NR₇R₈; and R₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula II in which A is —O—, R′ is OH; O—C₁-C₆ alkyl; or C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; R₁ is H; R₂ is 2-Cl, 2-Me, 2-CF₃, 3-F, 3-Me, 3-N(CH₃)₂; 3-C(O)OEt, 3-C(O)OMe, 4-Cl, or 4-OH; and R₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula II in which A is —O—, R′ is OH; O—C₁-C₆ alkyl; or C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; R₁ is 2-Me, 2-F, or 2-Cl; R₂ is 3-Me, 3-F, 3-Cl, 5-Me, 5-F, 5-Cl or 3-CF₃; and R₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula II in which A is —O—, R′ is OH; O—C₁-C₆ alkyl; or C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; R₁ is 5-Cl; R₂ is —C(O)NR₇R₈, or —S(O)₂NR₇R₈; and R₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula II in which A is —O—, R′ is —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups are optionally substituted with one to three groups selected independently from hydroxy, halogen, and methyl; R₁ is H; R₂ is 2-Cl, 2-Me, 2-CF₃, 3-F, 3-Me, 3-N(CH₃)₂; 3-C(O)OEt, 3-C(O)OMe, 4-Cl, or 4-OH; and R₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula II II in which A is —O—, R′ is —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups are optionally substituted with one to three groups selected independently from hydroxy, halogen, and methyl; R₁ is 2-Me, 2-F, or 2-Cl; R₂ is 3-Me, 3-F, 3-Cl, 5-Me, 5-F, 5-Cl or 3-CF₃; and R₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula II II in which A is —O—, R′ is —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups are optionally substituted with one to three groups selected independently from hydroxy, halogen, and methyl; R₁ is 5-Cl; R₂ is —C(O)NR₇R₈, or —S(O)₂NR₇R₈; and R₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula III

wherein A is —O—, —CH₂—, —N₂—, —CH₂C(O)—, —C(O)CH₂—, —S—, or —C(O)—; and substituents R¹-R′ are as defined for formula I.

In another embodiment, this invention provides a compound of formula III in which A is —O—.

In another embodiment, this invention provides a compound of formula III in which A is C(O), —CH₂—, or C(O)CH₂.

In another embodiment, this invention provides a compound of formula III in which A is —O—, and R′ is C₁-C₆ alkyl or C₃₋₆ cycloalkyl, all such C₁-C₆ alkyl and C₃₋₆ cycloalkyl optionally substituted with one to three OH groups.

In another embodiment, this invention provides a compound of formula III in which A is —O—; and R′ is —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₆ cycloalkyl, phenyl, pyridyl, piperazin-1-yl, piperidin-1-yl, N-morpholyl, tetrahydrofuryl, and naphthyl.

In another embodiment, this invention provides a compound of formula III in which A is —O—; and R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl, 3-hydroxypropyl, or 2,3-dihydroxypropyl.

In another embodiment, this invention provides a compound of formula III in which A is —O—; R′ is C₁-C₆ alkyl or C₃₋₆ cycloalkyl, all such C₁-C₆ alkyl and C₃₋₆ cycloalkyl optionally substituted with one to three OH groups; and R₄ is H, CH₃, or CF₃.

In another embodiment, this invention provides a compound of formula III in which A is —O—; R′ is —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₆ cycloalkyl, phenyl, pyridyl, piperazin-1-yl, piperidin-1-yl, N-morpholyl, tetrahydrofuryl, and naphthyl; and R₄ is H, CH₃, or CF₃.

In another embodiment, this invention provides a compound of formula III in which A is —O—; R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl, 3-hydroxypropyl, or 2,3-dihydroxypropyl; and R₄ is H, CH₃, or CF₃.

In another embodiment, this invention provides a compound of formula III in which A is —O—; R′ is C₁-C₆ alkyl or C₃₋₆ cycloalkyl, all such C₁-C₆ alkyl and C₃₋₆ cycloalkyl optionally substituted with one to three OH groups; and R₄ is F, Cl, or Br.

In another embodiment, this invention provides a compound of formula III in which A is —O; R′ is —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₆ cycloalkyl, phenyl, pyridyl, piperazin-1-yl, piperidin-1-yl, N-morpholyl, tetrahydrofuryl, and naphthyl; and R₄ is F, Cl, or Br.

In another embodiment, this invention provides a compound of formula III in which A is —O—; R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl, 3-hydroxypropyl, or 2,3-dihydroxypropyl; and R₄ is F, Cl, or Br.

In another embodiment, this invention provides a compound of formula III in which A is —O—; R′ is C₁-C₆ alkyl or C₃₋₆ cycloalkyl, all such C₁-C₆ alkyl and C₃₋₆ cycloalkyl optionally substituted with one to three OH groups; R₄ is H, CH₃, or CF₃; and R₅ is F.

In another embodiment, this invention provides a compound of formula III in which A is —O—; R′ is —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₆ cycloalkyl, phenyl, pyridyl, piperazin-1-yl, piperidin-1-yl, N-morpholyl, tetrahydrofuryl, and naphthyl; 4 is H, CH₃, or CF₃; and R₅ is F.

In another embodiment, this invention provides a compound of formula III in which A is —O—; R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl, 3-hydroxypropyl, or 2,3-dihydroxypropyl; R₄ is H, CH₃, or CF₃; and R₅ is F.

In another embodiment, this invention provides a compound of formula III in which A is —O—; R′ is C₁-C₆ alkyl or C₃₋₆ cycloalkyl, all such C₁-C₆ alkyl and C₃₋₆ cycloalkyl optionally substituted with one to three OH groups; R₄ is F, Cl, or Br; and R₅ is F.

In another embodiment, this invention provides a compound of formula III in which A is —O—; R′ is —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₆ cycloalkyl, phenyl, pyridyl, piperazin-1-yl, piperidin-1-yl, N-morpholyl, tetrahydrofuryl, and naphthyl; R₄ is F, Cl, or Br; and R₅ is F.

x14 In another embodiment, this invention provides a compound of formula III in which A is —O—; R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl, 3-hydroxypropyl, or 2,3-dihydroxypropyl; R₄ is F, Cl, or Br; and R₅ is F.

x14 sub: In another embodiment, this invention provides a compound of formula III in which A is —O—, R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl, 3-hydroxypropyl, or 2,3-dihydroxypropyl, R₁ is H, and R₂ is selected from 2-Cl, 2-Me, 2-CF₃, 3-F, 3-Me, 3-N(CH₃)₂; 3-C(O)OEt, 3-C(O)OMe, 4-Cl, and 4-OH.

In another embodiment, this invention provides a compound of formula III in which A is —O—, R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl, 3-hydroxypropyl, or 2,3-dihydroxypropyl, R₁ is H, and R₂ is 2-Cl, 2-Me, 2-CF₃, 3-F, 3-Me, 3-N(CH₃)₂, 3-C(O)OEt, 3-C(O)OMe, 4-Cl, or 4-OH.

In another embodiment, this invention provides a compound of formula III in which A is —O—, R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl, 3-hydroxypropyl, or 2,3-dihydroxypropyl, R₁ is 2-Me, 2-F, or 2-Cl; and R₂ is 3-Me, 3-F, 3-Cl, 5-Me, 5-F, 5-Cl or 3-CF₃.

In another embodiment, this invention provides a compound of formula III in which A is —O—, R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl, 3-hydroxypropyl, or 2,3-dihydroxypropyl, R₁ is 5-Cl; and R₂ is —C(O)NR₇R₈, or —S(O)₂NR₇R₈.

In another embodiment, this invention provides a compound of formula III in which A is —O—, R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl, 3-hydroxypropyl, or 2,3-dihydroxypropyl, R₁ is 2-Me, 2-F, or 2-C₁ and R₂ is 4-F, 4-Cl, 4-1,4-CF₃.

In another embodiment, this invention provides a compound of formula III in which A is —O—, R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl, 3-hydroxypropyl, or 2,3-dihydroxypropyl, R₁ is 3-Me or 3-F and R₂ is 5-F, 5-Me or 5-CF₃.

In another embodiment, this invention provides a compound of formula III in which A is —O—, R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl, 3-hydroxypropyl, or 2,3-dihydroxypropyl, R_(1,2) are 2-Cl and 5-Cl, R_(4,5) are 2-F and 5-F, and R₆ is H.

In another embodiment, this invention provides a compound of formula III in which A is O; R′ is —CH(CH₂OH)CH₂D, where D is selected from imidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, and adamantin-1-yl; R₁ is 2-Me, 2-F, or 2-Cl; and R₂ is 3-Me, 3-F, 3-Cl, 5-Me, 5-F, 5-Cl or 3-CF₃.

In another embodiment, this invention provides a compound of formula III in which A is O; R′ is —CH(CH₂OH)CH₂D, where D is selected from imidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, and adamantin-1-yl; R₁ is 5-Cl; and R₂ is —C(O)NR₇R₈, or —S(O)₂NR₇R₈,

In another embodiment, this invention provides a compound of formula III in which A is O; R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is a five- or six-membered ring or a 9-14-membered fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds; R₁ is H; and R₂ is 2-Cl, 2-Me, 2-CF₃, 3-F, 3-Me, 3-N(CH₃)₂; 3-C(O)OEt, 3-C(O)OMe, 4-Cl, or 4-OH.

In another embodiment, this invention provides a compound of formula III in which A is O and R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is a five- or six-membered ring or a 9-14-membered fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds; R₁ is 2-Me, 2-F, or 2-Cl; and R₂ is 3-Me, 3-F, 3-Cl, 5-Me, 5-F, 5-Cl or 3-CF₃.

In another embodiment, this invention provides a compound of formula III in which A is O, R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is a five- or six-membered ring or a 9-14-membered fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds; R₁ is 5-Cl; and R₂ is —C(O)NR₇R₈, or —S(O)₂NR₇R₈,

In another embodiment, this invention provides a compound of formula III in which A is —O—, R′ is OH; O—C₁-C₆ alkyl; or C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; R₁ is H and R₂ is 2-Cl, 2-Me, 2-CF₃, 3-F, 3-Me, 3-N(CH₃)₂; 3-C(O)OEt, 3-C(O)OMe, 4-Cl, or 4-OH.

In another embodiment, this invention provides a compound of formula III in which A is —O—, R′ is OH; O—C₁-C₆ alkyl; or C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; R₁ is 2-Me, 2-F, or 2-Cl; and R₂ is 3-Me, 3-F, 3-Cl, 5-Me, 5-F, 5-Cl or 3-CF₃.

In another embodiment, this invention provides a compound of formula III in which A is —O—, R′ is OH; O—C₁-C₆ alkyl; or C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; R₁ is 5-Cl; and R₂ is —C(O)NR₇R₈, or —S(O)₂NR₇R₈.

In another embodiment, this invention provides a compound of formula III in which A is —O—, R′ is —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups are optionally substituted with one to three groups selected independently from hydroxy, halogen, and methyl; R₁ is H; and R₂ is 2-Cl, 2-Me, 2-CF₃, 3-F, 3-Me, 3-N(CH₃)₂; 3-C(O)OEt, 3-C(O)OMe, 4-Cl, or 4-OH.

In another embodiment, this invention provides a compound of formula III in which A is —O—, R′ is —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups are optionally substituted with one to three groups selected independently from hydroxy, halogen, and methyl; R₁ is 2-Me, 2-F, or 2-Cl; and R₂ is 3-Me, 3-F, 3-Cl, 5-Me, 5-F, 5-Cl or 3-CF₃.

In another embodiment, this invention provides a compound of formula III in which A is —O—, R′ is —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups are optionally substituted with one to three groups selected independently from hydroxy, halogen, and methyl; R₁ is 5-Cl; and R₂ is —C(O)NR₇R₈, or —S(O)₂NR₇R₈

In another embodiment, this invention provides a compound of formula IV

wherein U, V, W, X, Y, and Z are, independently CH or N, provided that U, V, W, X, Y, and Z are not all CH; A is —O—, —CH₂—, —N₂—, —NHC(O)—, —CH₂C(O)—, —C(O)CH₂—, —S—, or —C(O)—; R₁ and R₂ are, independently, hydrogen; halogen; hydroxy; cyano; CH₃, optionally substituted with 1-3 fluorine atoms; CH₃O; (CH₃)₂N; CH₃OC(O); 2-methoxy ethenyl; and CH₃CH₂OC(O); and R′ is OH; OC₁-C₆ alkyl; C₁-C₆ alkyl, optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups are optionally substituted with one to three groups selected independently from hydroxy, halogen, and methyl.

In a more specific embodiment, this invention provides a compound of formula IV, in which A is —O—, —CH₂—, —NHC(O)—, —S—, or —C(O)—.

In another embodiment, this invention provides a compound of formula V

wherein U and X are, independently CH or N, provided that U and X are not both CH; R₁ and R₂ are, independently, hydrogen; halogen; hydroxy; cyano; CH₃, optionally substituted with 1-3 fluorine atoms; CH₃O; (CH₃)₂N; CH₃OC(O); 2-methoxy ethenyl; and CH₃CH₂OC(O); and R′ is selected from C₁-C₆ alkyl, optionally substituted with 1-3 hydroxyl groups; cyclopropyl; —CH₂B; and —CH₂CH₂B, where B is selected from C₃₋₆ cycloalkyl, phenyl, pyridyl, piperzin-1-yl, piperidin-1-yl, N-morpholyl, tetrahydrofuryl, and naphthyl.

In still another embodiment, this invention provides a compound of formula VI

where Y is —NH—, —S— or —O—, and R₁—R′ are defined as for formula II.

In a more specific embodiment, this invention provides a compound of formula VIa, where Y is —NH—, —S— or —O—,

In a more specific embodiment, this invention provides a compound of formula VIa where Y is —S— or —O—, and R′ is selected from 1-hydroxy-isopropyl, 2-hydroxy-n-propyl, 2-hydroxy-ethyl, and 2,3,-dihydroxy-n-propyl.

In another generic embodiment, this invention provides a compound of formula VII

where the dashed bond represents an optional double bond, and where symbols T-Z represent N, CH, or CR_(1, 2, or 4), provided that at most two of W, X, Y, and Z and at most 2 of T, U, and V are N; where R₁-R₄ are defined as for formula I; and where R′ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; or R′ is —(CH₂)_(n)—B where n is 1 or 2 and B is defined as above.

In one subgeneric embodiment, this invention provides a compound of formula VIIa,

where R₁-R₄ and R′ are defined as for formula I.

In a more specific embodiment, this invention provides a compound of formula VIIa where R₁ is defined as in formula II, R₃ and R₄ are both H and R′ is —(CH₂)_(n)—B, where n is 1 or 2 and B is defined as above.

In another more specific embodiment, this invention provides a compound of formula VIIa where R₃ and R₄ are both H and R′ is C₁-C₆ alkyl or O—C₁-C₆ alkyl, both optionally substituted as described above.

In another more specific embodiment, this invention provides a compound of formula VIIa, where R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula VIIa, where R₂—R are H and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl, 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In another subgeneric embodiment, this invention provides a compound of formula VIIA in which R₁ is isothiazolyl, isoxazolyl, oxazolyl, oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl; R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, pyrimidyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl; oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolyl, isothiazolinyl, isothiazolidinyl, isothiazolidinonyl, indolyl, indolyl, oxindolyl, isoindolyl, quinolyl, isoquinolyl, and naphthyl.

In a still more specific embodiment, this invention contemplates the compound of formula VIIA in which R₁ is 2-fluoro, -chloro, -bromo, -methyl, -trifluoromethyl, -methoxy, or -hydroxy; R₂, R₃, and R₄ are H; and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a another more specific embodiment, this invention contemplates the compound of formula VIIA in which R₁ is 3-fluoro, -chloro, -bromo, -methyl, -trifluoromethyl, -methoxy, or -hydroxy; R₂, R₃, and R₄ are H; and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a another more specific embodiment, this invention contemplates the compound of formula VIIA in which R₁ is 4-fluoro, -chloro, -bromo, -methyl, -trifluoromethyl, -methoxy, or -hydroxy; R₂, R₃, and R₄ are H; and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a another more specific embodiment, this invention contemplates the compound of formula VIIA in which R₁ is 5-fluoro, -chloro, -bromo, -methyl, -trifluoromethyl, -methoxy, or -hydroxy; R₂, R₃, and R₄ are H; and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In another subgeneric embodiment, this invention provides a compound of formula VIIA-1, where R₁—R′ are defined as for formula A.

In a more specific embodiment, this invention provides a compound of formula VIIA-1 where R₁-R₄ are H and R′ is isopropyl, 2-butyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another generic embodiment, this invention provides a compound of formula VII, in which at least one of T, U, V, W, X, Y, and Z is N.

In another generic embodiment, this invention provides a compound of formula VII, in which at least one of W, X, Y, and Z is N.

In another generic embodiment, this invention provides a compound of formula VII, in which at least one of T, U, and V is N.

In another generic embodiment, this invention provides a compound of formula VII, in which two of W, X, Y, and Z are N.

In another generic embodiment, this invention provides a compound of formula VII, in which one of T, U, and V and one of W, X, Y, and Z are N.

In another generic embodiment, this invention provides a compound of formula VIIB

where substituents are defined as for formula II.

In a subgeneric embodiment, this invention provides a compound of formula VIIB-1

In a more specific embodiment, this invention provides a compound of formula VIIB-1, where R₁-R₄ are, independently, H, C₁-C₃ alkyl, or halogen, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In another more specific embodiment, this invention provides a compound of formula VIIB-1, where R₁-R₄ are H and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound of formula VIIB-1 where one of R₁ and R₂ is H and the other is amino, methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino, R₃-R₄ are H, and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula VIIB-1, where one of R₁ and R₂ is H and the other is nitro, cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl, R₃-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula VIIB-1, where R₁ and R₂ are fused cyclohexyl or fused cyclopentyl, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound of formula VIIB-1, where R₁ and R₂ are benzo, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound of formula VIIB-1, wherein R₁ and R₂ are halogen, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In a more specific embodiment, this invention provides a compound of formula VIIB-1, where R₁-R₃ are H, R₄ is 2-halo, 2-cyano, 2-hydroxy, or 2-methoxy, and R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In another more specific embodiment, this invention provides a compound of formula VIIB-1, where R₁ is halo, R₂-R₄ are H and R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, the invention contemplates a compound of formula VIIB-1, where R₁ is bromo, R₂-R₄ are H and R′ is isopropyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, or 2,3-dihydroxy-1-propyl.

In a subgeneric embodiment, this invention provides a compound of formula VIIB-2

In a more specific embodiment, this invention provides a compound of formula VIIB-2, where R₁-R₄ are, independently, H, C₁-C₃ alkyl, or halogen, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In another more specific embodiment, this invention provides a compound of formula VIIB-2, wherein R₁ and R₂ are halogen, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In a still more specific embodiment, the invention contemplates a compound of formula VIIB-2, where R₁ is bromo, R₂-R₄ are H and R′ is 2-cyclopropyl ethyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, or 2,3-dihydroxy-1-propyl.

In another more specific embodiment, the invention contemplates a compound of formula VIIB-2, where R₁ and R₂ are fused (2,3) pyrido, R₄ is 2-chloroethyl, and R′ is 2-cyclopropyl ethyl, 2-hydroxyethyl, or 2-cyclopenylethyl.

In another more specific embodiment, the invention contemplates a compound of formula VIIB-2, where R₁ and R₂ are fused (2,3) pyrrolo, fused (2,3) furyl, or fused (4,5) imidazolo, R₄ is H, and R′ is 2-hydroxyethyl, or isopropyl.

Additional embodiments of generic structures with one or more of T-Z=nitrogen are shown below, together with a contemplated compound for each generic structure. These contemplated compounds indicate the range of contemplated substituents. Generic Structure Example

VIIB-3 VIIB-3a

VIIB-4 VIIB-4a

VIIB-5 VIIB-5a

VIIB-6 VIIB-6a

VIIB-7 VIIB-7a

VIIB-8 VIIB-8a

VIIB-9 VIIB-9a

VIIB-10 VIIB-10a

VIIB-11 VIIB-11a

VIIB-12 VIIB-12a

VIIB-13 VIIB-13a

VIIB-14 VIIB-14a

VIIB-15 VIIB-15a

VIIB-16 VIIB-16a

VIIB-17 VIIB-17a

VIIB-18 VIIB-18a

VIIB-19 VIIB-19a

VIIB-20 VIIB-20a

VIIB-21 VIIB-21a

VIIB-22 VIIB-22a

VIIB-23 VIIB-23a

VIIB-24 VIIB-24a

VIIB-25 VIIB-25a

VIIB-26 VIIB-26a

VIIB-27 VIIB-27a

VIIB-28 VIIB-28a

VIIB-29 VIIB-29a

VIIB-30 VIIB-30a

VIIB-31 VIIB-31a

VIIB-32 VIIB-32a

VIIB-33 VIIB-33a

VIIB-34 VIIB-34a

VIIB-35 VIIB-35a

VIIB-36 VIIB-36a

VIIB-37 VIIB-37a In additional embodiments, the invention provides compounds according to any of formulas VIIB-3 to VIIB-37, wherein R₁-R₄ are all independently methyl, methoxy, ethyl, vinyl, ethynyl, halo, or H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl, cyclohexyl, or cyclohexen-2-yl.

In additional more specific embodiments, the invention provides compounds according to any of formulas VIIB-3 to VIIB-37, wherein R₁-R₄ are all independently halo, halomethyl, or H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is phenyl, pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In additional more specific embodiments, the invention provides compounds according to any of formulas VIIB-3 to VIIB-37, wherein R₁-R₄ are all independently halo, halomethyl, or H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is quinolyl, thiazolidinonyl, isothiazolidinonyl, or oxindolyl.

In additional more specific embodiments, the invention contemplates compounds according to any of formulas VIIB-3 to VIIB-37, where R₁ is bromo, R₂-R₄ are H, and R′ is isopropyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In additional more specific embodiments, the invention contemplates compounds according to any of formulas VIIB-3 to VIIB-37, where R₁-R₄ are H and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

In additional more specific embodiments, the invention contemplates compounds according to any of formulas VIIB-3 to VIIB-37, where R₁ is propyn-3-yl, R₂-R₄ are H and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

In additional more specific embodiments, the invention contemplates compounds according to any of formulas VIIB-3 to VIIB-37, where R₁ is nitro or cyano, R₂-R₄ are H and R′ is 2-hydroxyethyl or 2-hydroxypropyl.

In additional more specific embodiments, the invention contemplates compounds according to any of formulas VIIB-3 to VIIB-37, where R₂ is dimethylamino or dimethylaminomethyl, R₁, R₃, and R₄ are H and R′ is isobutyl or 3-cyclopentyl-propyl.

In still more specific embodiments, the invention contemplates compounds according to any of formulas VIIB-3 to VIIB-37, where R₁-R₃ are H, R₄ is chloro, and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

In still more specific embodiments, the invention contemplates compounds according to any of formulas VIIB-3 to VIIB-37, where R₂ is bromo, R₁, R₃, and R₄ are H, and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

Additional contemplated compounds for generic embodiments of formula VII are shown in the tables below. Cpd Structure 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

In another generic embodiment, this invention provides a compound of formula VIII below,

where the dashed bond represents an optional double bond, where symbols W-Z represent N, CH, or CR_(1 or 2), and where R₁-R′ are, defined as for formula VII.

In one subgeneric embodiment, this invention provides a compound of formula VIIIA below,

where the dashed bond represents an optional double bond, and where all substituents are defined as for formula VIII.

In another generic embodiment, this invention provides a compound of formula VIIIB,

where the dashed bond represents an optional double bond, where all substituents are defined as for formula VIII, and where symbols W-Z represent N, CH, or CR_(1 or 2), provided that at least one of W-Z is N. In one subgeneric embodiment, this invention provides a compound of formula VIIIA-1,

where all substituents are defined as for formula VIII.

In a more specific embodiment, this invention provides a compound of formula VIIIA-1, where R₁ and R₂ are as described above for formula VIII; R₃ and R₄ are both H; and R′ is —(CH₂)_(n)—B, where n is 1 or 2 and B is a five- or six-membered ring or a 9- to 14-member fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, where R₁ and R₂ are as described above; R₃ and R₄ are both H; and R′ is C₁-C₆ alkyl or O—C₁-C₆ alkyl, both optionally substituted as described above.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, where R₁ and R₂ are as described above; R₃ and R₄ are both H and R′ is C₁-C₆ alkyl or O—C₁-C₆ alkyl, both optionally substituted as described above.

In a still more specific embodiment, this invention provides a compound of formula VIIIA-1, where R₁-R₄ are H and R′ is C₁-C₆ alkyl or O—C₁-C₆ alkyl, both optionally substituted as described above.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are halogen; R₃ and R₄ are H; and R′ is methyl, ethyl, isopropyl, or sec-butyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ is halogen; R₂-R₄ are H; and R′ is methyl, ethyl, isopropyl, or sec-butyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are halogen; R₃ and R₄ are H; and R′ is 1,2-chloropropan-3-yl or 1-hydroxy-butan-3-yl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ is bromo; R₂-R₄ are H; and R′ is isopropyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are halogen; R₃ and R₄ are H; and R′ is 1,2-dihydroxy-propan-3-yl, 2-hydroxyethyl, 1,2-dihydroxybutan-4-yl, or 4-hydroxybutyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are halogen; R₃ and R₄ are C₁-C₆ alkyl; and R′ is 1,2-dihydroxybutan-3-yl or 4-methoxybutyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are 5-chloro and 6-chloro; R₃ and R₄ are H; and R′ is 3-hydroxypropyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are H; R₃ is 2-hydroxy; R₄ is H; and R′ is 3-hydroxypropyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are 5-chloro and 6-chloro; R₃ is 2-hydroxy; R₄ is H; and R′ is 3-hydroxypropyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are, independently, H or halogen; R₃ is H, 2-OH, or 2-methyl; R₄ is H or methyl; and R′ is 1,2-chloropropan-3-yl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are halogen; R₃ and R₄ are, independently H, OH, or methyl; and R′ is 1-hydroxy-butan-3-yl, 1,2-dihydroxy-propan-3-yl, or 2-hydroxyethyl

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ is halo; R₂-R₄ are, independently H, OH, or methyl; and R′ is isopropyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are, independently, H or halogen; R₃ and R₄ are, independently, H, OH, or methyl; and R′ is 4-hydroxybutyl or 1,2-dihydroxybutan-4-yl

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are, independently, H or halogen; R₃ and R₄ are, independently, H, OH, or methyl; and R′ is 1,2-dihydroxybutan-3-yl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are, independently, H, C₁-C₆ alkyl, C₁-C₆ alkenyl, C₁-C₆ cycloalkyl, or halogen; R₃ and R₄ are, independently, H, OH, or C₁-C₆ alkyl; and R′ is 1,2-dihydroxybutan-3-yl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are, independently, H, C₁-C₆ alkyl, or halogen; R₃ and R₄ are, independently, H, OH or methyl; and R′ is 4-methoxybutyl, 3-hydroxypropyl or 2-hydroxypropyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, where R₁ and R₂ are fused cyclohexyl or fused cyclopentyl; R₃ and R₄ are, independently, H, OH, or methyl; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, where R₁ and R₂ are benzo; R₃ and R₄ are, independently, H, OH, or methyl; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula VIIIA-1, where R₁ and R₂, at positions 4 and 5, are fused (4,5)-imidazolo; R₃ and R₄ are, independently, H, OH, or methyl; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula VIIIA-1, where R₁ and R₂, at positions 5 and 6, are fused (2,3)-furyl, (2,3)-pyridyl, or fused cyclopentyl; R₃ and R₄ are, independently, H, OH, or methyl; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula VIIIA-1, where R₁ and R₂, at positions 5 and 6, are fused cyclopentyl; R₃ and R₄ are, independently, H, OH, or methyl; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula VIIIA-1, where R₁ and R₂, at positions 6 and 7, are fused cyclopentyl, R₃ and R₄ are, independently, H, OH, or methyl; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula VIIIA-1, where R₁ and R₂, at positions 5 and 6, are benzo; R₃ and R₄ are, independently, H, OH, or methyl; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula VIIIA-1, where R₁ and R₂, at positions 6 and 7, are benzo; R₃ and R₄ are, independently, H, OH, or methyl; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula VIIIA-1, where R₁ and R₂, at positions 4 and 5, are benzo, said benzo group bearing fluoro at each ortho position; R₃ and R₄ are, independently, H, OH, or methyl; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, where R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In a still more specific embodiment, this invention provides a compound of formula VIIIA-1, where R₁-R₄ are H and R′ is C₁-C₄ alkyl, optionally substituted with one or two hydroxy groups.

In another still more specific embodiment, this invention provides a compound of formula VIIIA-1, where R₁, R₂, and R₄ are H; R₃ is methyl or OH; and R′ is C₁-C₄ alkyl, optionally substituted with one or two hydroxy groups.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, where R₁ and R₂ are H; R₃ is H, methyl, or OH; R₄ is H, OH, or C₁-C₄ alkyl, optionally substituted with halogen or hydroxy; and R′ is C₁-C₄ alkyl, optionally substituted with one or two hydroxy groups.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, where R₁ and R₂ are H; R₃ is H, methyl, or OH; R₄ is methyl, optionally substituted with halogen or hydroxy; and R′ is C₁-C₄ alkyl, optionally substituted with one or two hydroxy groups.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, where R₁ and R₂ are H; R₃ is H, methyl, or OH; R₄ is C₁-C₄ alkyl, optionally substituted with halogen or hydroxy; and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, where R₁ is amino, methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino, R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, where R₁ is nitro, cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl, R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In a still more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are both halogen, R₃ is 2-methyl, and R₄ is H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is 2-chloro, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is 2-(2-chloroethyl), and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ is 4-CF₃, R₃ is 2-hydroxymethyl, R₂ and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is 2-chloro, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula VIIIA-1, in which one or both of R₁ and R₂ are CF₃, R₃ and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ is isothiazolyl, isoxazolyl, oxazolyl, oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl; R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, pyrimidinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl; oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolyl, isothiazolinyl, isothiazolidinyl, isothiazolidinonyl, indolyl, indolyl, oxindolyl, isoindolyl, quinolyl, isoquinolyl, and naphthyl.

In a still more specific embodiment, this invention contemplates the compound of formula VIIIA-1, in which R₁ is 6-chloro, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula VIIIA-1, in which R₁ is 5-chloro, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula VIIIA-1, in which R₁ is 4-chloro, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula VIIIA-1, in which R₁ is 7-chloro, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula VIIIA-1, in which R₁ is 7-bromo, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula VIIIA-1, in which R₁ is 4-bromo, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula VIIIA-1, in which R₁ is 5-bromo, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates a compound of formula VIIIA-1, in which R₁ is 5-CF₃, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂, in positions 4 and 6, are both halogen, R₃ is 2-chloromethyl, and R₄ is H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-piperidyl, 3-piperidyl, or 4-piperidyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂, in positions 4 and 6, are both halogen, R₃ is 3-fluoromethyl, and R₄ is H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is 2-pyrimidyl, 4-pyrimidyl, 2-morpholyl, or 3-morpholyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ and R₂, in positions 4 and 6, are both halogen, R₃ is 3-fluoromethyl, and R₄ is H, and R′ is —(CH₂)_(n)—B, where n is 2, and B is 4-bromo-2-pyrimidyl, 2-chloro-4-pyrimidyl, 2-morpholyl, or 3-morpholyl.

In a still more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ is 3-cyano, R₂-R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula VIIIA-1, in which R₁ is 3-hydroxy, 5-dimethylamino, 4-methoxy, 5-(2-methoxyethyl), or 6-methoxymethyl R₂-R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention contemplates a compound of formula VIIIA-1, in which R₁ is 4-ethoxy, 4-cyano, 4-CH₂F, 7-acetoxy, 7-acetyl, 6-methyloxycarbonyl, 6-dimethylaminocarbonyl, 4-dimethylamino, 5-dimethylaminocarbonyl, 5-methyloxycarbonyl, 4-acetyl, 4-acetoxy, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl. In another embodiment, this invention provides a compound of formula VIIIA-2

In a more specific embodiment, this invention provides a compound of formula A-2, where R₃ and R₄ are both H and R′ is —(CH₂)_(n)—B.

In another subgeneric embodiment, this invention provides a compound of formula VIIIA-2, where R′ is C₁-C₆ alkyl or O—C₁-C₆ alkyl, both optionally substituted as described above.

In another subgeneric embodiment, this invention provides a compound of formula VIIIA-2, where R₃ and R₄ are both H and R′ is C₁-C₆ alkyl or O—C₁-C₆ alkyl, both optionally substituted as described above.

In a more specific embodiment, this invention provides a compound of formula VIIIA-2, where R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another still more specific embodiment, this invention provides a compound of formula A-1, where R₁, R₂, and R₄ are H; R₃ is H, methyl or OH; and R′ is C₁-C₄ alkyl, optionally substituted with one or two hydroxy groups.

In another more specific embodiment, this invention provides a compound of formula A-1, where R₁ and R₂ are H; R₃ is H, methyl, or OH; R₄ is C₁-C₄ alkyl, optionally substituted with halogen or hydroxy; and R′ is C₁-C₄ alkyl, optionally substituted with one or two hydroxy groups.

In another more specific embodiment, this invention provides a compound of formula VIIIA-2, where R₁, in position 5, is dimethylamino, dimethylaminomethyl, or acetylamino, R₃, in position 3, is methoxy or methoxymethyl, R₂ and R₄ are H, and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula VIIIA-2, where R₁, in position 4, is dimethylamino, dimethylaminomethyl, or acetylamino, R₂, in position 6, is bromomethyl, R₃ and R₄ are H, and R′ is mono-hydroxy C₁-C₄ alkyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-2, where R₁ is nitro, cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl, R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula VIIIA-2, in which R₁ and R₂ are both halogen, R₃ is 2-methyl, and R₄ is H, and R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-2, in which R₁ and R₂, in positions 4 and 6, are both halogen, R₃ is 2-chloromethyl, and R₄ is H, and R′ is —(CH₂)_(n)—B, where n is 1, and B is 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-piperidyl, 3-piperidyl, or 4-piperidyl.

In another more specific embodiment, this invention provides a compound of formula VIIIA-2, in which R₁ and R₂, in positions 4 and 6, are both halogen, R₃ is 3-fluoromethyl, and R₄ is H, and R′ is —(CH₂)_(n)—B, where n is 1, and B is 2-pyrimidyl, 4-pyrimidyl, 2-morpholyl, or 3-morpholyl.

In a more specific embodiment, this invention contemplates a compound of formula VIIIA-2, where R₁-R₄ are H and R′ is 2-(2-furyl)ethyl, 2-hydroxyethyl, or 2,3-dihydroxy-1-propyl.

In another more specific embodiment, this invention contemplates a compound of formula VIIIA-2 in which R₁ and R₂ together, at positions 5 and 6, are benzo or fused cyclopentyl, R₃ and R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention contemplates a compound of formula VIIIA-2 in which R₁ and R₂ together, at positions 6 and 7, are fused 2,3-pyrido or pyrrolo, R₃ and R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention contemplates a compound of formula VIIIA-2 in which R₁ and R₂ together, at positions 4 and 5, are fused (2,3)-furyl, R₃ and R₄ are H, and R′ is 1,2-dihydroxy-propan-3-yl.

In another more specific embodiment, this invention contemplates a compound of formula VIIIA-2 in which R₁ and R₂ together, at positions 6 and 7, are fused (2,3)thienyl, R₃ and R₄ are H, and R′ is 2-hydroxyethyl.

In a still more specific embodiment, this invention provides a compound of formula VIIIA-2 in which R₁ and R₂ are both H, R₃ is 4-methyl or 5-methyl, R₄ is 7-chloro, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula VIIIA-2 in which R₁ is 4-CF₃, R₃ is 6-hydroxymethyl, R₂ and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula VIIIA-2 in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is 2-chloro, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula VIIIA-2 in which R₁ is 5-chloro, 6-chloro, or 7-chloro, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula VIIIA-2 in which R₁ is 3-bromo, 4-bromo, or 5-bromo, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula VIIIA-2 in which R₁ is 6-chloro, R₂ is 7-chloro, R₃ and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula VIIIA-2 in which one or both of R₁ and R₂ are CF₃, R₃ and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula VIIIA-2 in which R₁ is 4-CF₃, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula VIIIA-2 in which R₁ is 4-cyano, 4-hydroxy, 4-methoxy, 5-hydroxy, or 4-methoxymethyl, R₂-R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention contemplates a compound of formula VIIIA-2 in which R₁ is 4-dimethylamino, 7-acetyl, 7-dimethylamino, 7-dimethylaminocarbonyl, or 7-methyloxycarbonyl, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazol-4-yl, isoxazol-3-yl, oxazol-2-yl, 2-oxazolin-2-yl, oxazolidin-4-yl, thiazol-2-yl, thien-2-yl, fur-2-yl, pyrrol-3-yl, pyrrolin-4-yl, pyrrolidin-3-yl, thiazolin-4-yl, thiazolidin-4-yl, imidazol-2-yl, 2-pyridyl, 4-pyridyl, m-tolyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula VIIIA-2 in which R₁ is 6-acetoxy, or 7-acetoxy, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula VIIIA-2 in which R₁ is 7-acetyl, or 7-acetoxy, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula VIIIA-2 in which R₁ is 3-CH₂F, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

The following are subgeneric embodiments, as well as more specific embodiments and prophetic examples, which contain one or more of W-Z=nitrogen.

In one subgeneric embodiment, this invention provides a compound of formula VIIIB-1,

where all substituents are defined as for formula VIIIA.

In a more specific embodiment, this invention provides a compound of formula VIIIB-1, where R₁-R₄ are, independently, H, C₁-C₃ alkyl, OH, or halogen; and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compound of formula VIIIB-1, where R₁-R₄ are, independently, H, C₁-C₃ alkyl, OH, or halogen; and R′ is C₁-C₄ alkyl, optionally substituted with one or two hydroxy groups.

In a still more specific embodiment, this invention provides a compound of formula VIIIB-1, where R₁-R₄ are H and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In a specific contemplated example, this invention provides a compound of formula VIIIB-1, where R₁-R₄ are H and R′ is 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or isopropyl.

In a specific contemplated example, this invention provides a compound of formula VIIIB-1, where R₁ and R₂ are H; R₃ is 2-methyl or 2-hydroxy; R₄ is H or methyl; and R′ is isopropyl.

In another specific contemplated example, this invention provides a compound of formula VIIIB-1, where R₁ and R₂ are H; R₃ is 2-methyl or 2-hydroxy; R₄ is H or methyl; and R′ is 2,3-dihydroxy-1-propyl or 1-hydroxy-2-propyl.

In another specific contemplated example, this invention provides a compound of formula VIIIB-1, where R₁ is C₁-C₄ alkyl, C₁-C₄ alkenyl, C₁-C₄ alkynyl, halomethyl, or halogen; R₂-R₄ are H; and R′ is 3,4-dihydroxy-2-butyl.

In another specific contemplated example, this invention provides a compound of formula VIIIB-1, where R₁ is C₁-C₄ alkyl, C₁-C₄ alkenyl, C₁-C₄ alkynyl, halomethyl, or halogen; R₂— is H; R₃ is 2-OH; R₄ is methyl or H; and R′ is 3,4-dihydroxy-2-butyl.

In another specific contemplated example, this invention provides a compound of formula VIIIB-1, where R₁-R₄ are H and R′ is 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula VIIIB-1, where R₁-R₄ are H and R′ is ethoxy, isopropoxy, or O—CH(CH₃)CH₂CH₃.

In another specific contemplated example, this invention provides a compound of formula VIIIB-1, where R₁-R₄ are H and R′ is ethoxy.

In another more specific embodiment, this invention contemplates a compound of formula VIIIB-1, where R₁-R₄ are H and R′ is 2-chloroethyl, 2-bromoethyl, or 1,2-dichloro-3-propyl.

In another more specific embodiment, this invention provides a compound of formula VIIIB-1 where one of R₁ and R₂ is H and the other is amino, methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino, R₃-R₄ are H, and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula VIIIB-1, where one of R₁ and R₂ is H and the other is nitro, cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl, R₃-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula VIIIB-1, where R₁ and R₂ are fused cyclohexyl or fused cyclopentyl, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound of formula VIIIB-1, where R₁ and R₂ are benzo, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound of formula VIIIB-1, wherein R₁ and R₂ are halogen, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In a more specific embodiment, this invention provides a compound of formula VIIIB-1, where R₁-R₃ are H, R₄ is 2-halo, 2-cyano, 2-hydroxy, or 2-methoxy, and R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compound of formula VIIIB-1, where R₁ is halo, R₂-R₄ are H and R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, the invention contemplates a compound of formula VIIIB-1, where R₁ is bromo, R₂-R₄ are H and R′ is isopropyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, or 2,3-dihydroxy-1-propyl.

In another embodiment, this invention provides a compound of formula VIIIB-2,

where substituents are defined as for formula I.

In a more specific embodiment, this invention provides a compound of formula VIIIB-2, where R₁-R₄ are, independently, H or halogen, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2-methoxyethyl, 1-hydroxy-2-propyl,1,2-dihydroxy-3-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound of formula VIIIB-2, where one of R₁ and R₂ is H and the other is amino, methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino, R₃-R₄ are H, and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula VIIIB-2, where one of R₁ and R₂ is H and the other is nitro, cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl, R₃-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

Additional subgeneric embodiments of compounds of formula I with one or more of W-Z=nitrogen are shown below.

In more specific embodiments, the invention provides compounds according to any of formulas VIIIB-3 to VIIIB-20, wherein R₁-R₄ are all independently methyl, methoxy, ethyl, vinyl, ethynyl, halo, OH, or H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In additional more specific embodiments, the invention provides compounds according to any of formulas VIIIB-1 to VIIIB-20, wherein R₁-R₄ are all independently halo, halomethyl, OH, or H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is phenyl, pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In additional more specific embodiments, the invention contemplates compounds according to any of formulas VIIIB-1 to VIIIB-20, where R₁ is bromo; R₂-R₄ are all H; and R′ is isopropyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In still more specific embodiments, the invention contemplates compounds according to any of formulas VIIIB-1 to VIIIB-20, where R₁-R₄ are, independently, H, OH, C₁-C₄ alkyl, C₁-C₄ alkenyl, C₁-C₄ alkynyl, halo, halomethyl, nitro, or cyano; and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

In still more specific embodiments, the invention contemplates compounds according to any of formulas VIIIB-1 to VIIIB-20, where R₁-R₄ are all H and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

In still more specific embodiments, the invention contemplates compounds according to any of formulas VIIIB-1 to VIIIB-20, where R₁-R₄ are H; R₃ and R₄ are, independently, H, methyl, or OH; and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

In still more specific embodiments, the invention contemplates compounds according to any of formulas VIIIB-1 to VIIIB-20, where R₁ is acetyl, acetoxy, acetamido, methylcarbamoyl, methylsulfonyl, methyloxycarbonyl, ethyloxycarbonyl, or cyclopropylethynyl; R₂-R₄ are all H; and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

In still more specific embodiments, the invention contemplates compounds according to any of formulas VIIIB-1 to VIIIB-20, where R₁ is acetyl, acetoxy, acetamido, methylcarbamoyl, methylsulfonyl, methyloxycarbonyl, ethyloxycarbonyl, or cyclopropylethynyl; R₂ is H; R₃ is 2-OH or 2-methyl; R₄ is H, OH, or methyl; and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

In still more specific embodiments, the invention contemplates compounds according to any of formulas VIIIB-1 to VIIIB-20, where R₁-R₃ are all H; R₄ is chloro; and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

In still more specific embodiments, the invention contemplates compounds according to any of formulas VIIIB-1 to VIIIB-20, where R₂ is bromo; R₁, R₃, and R₄ are all H; and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

A number of prophetic examples of compounds according to formulas VIIIB-1 to VIIIB-20 are shown below.

Still more prophetic examples of compounds of this invention are shown below:

In another generic embodiment, this invention provides a compound of formula IX,

where M, Q, T, U, and V represent N, CH, or CR_(1, 2, or 3), provided that no two nitrogen atoms are adjacent, where R₁-R₄ are, defined as for formula I.

In one subgeneric embodiment, this invention provides a compound of formula A below, where all substituents are as defined for formula I above.

In another embodiment, this invention provides a compound of formula IXB,

where M, Q, T, U, and V represent N, CH, or CR_(1, 2, or 3), provided that at least one of M, Q, T, U, and V is N, and further provided that no two nitrogen atoms are adjacent, and where R₁-R₄ are as defined as above. In one more specific embodiment, this invention provides a compound of formula IXA, where R₁-R₄ are defined as for formula IX, and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is isothiazolyl, isoxazolyl, isoxazolindinonyl, oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolinyl, isothiazolidinyl, isothiazolidinonyl, imidazolinyl, imidazolyl, pyridyl, tolyl, or phenyl, wherein all rings are optionally substituted as described above.

In another more specific embodiment, this invention provides a compound of formula IXA, where R₁ and R₂ are as defined for formula IX; R₃ and R₄ are both H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, where R is 2-chloro, R₂ is 6-methyl, and R₃—R′ are as defined for formula IXA.

In another more specific embodiment, this invention provides a compound of formula IXA, where R₁-R₄ are defined as for formula I, and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is naphthyl, quinolyl, isoquinolyl, indanyl, or benzimidazolyl, wherein all rings are optionally substituted as described above in the definition of G for formula I.

In another more specific embodiment, this invention provides a compound of formula IXA, where R₁-R₄ are defined as for formula I, and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is cyclopentyl, cyclohexyl, tetrahydrofuryl, tetrahydrothienyl, piperidyl, piperazinyl, or morpholyl, wherein all rings are optionally substituted as with methyl or halo.

In another more specific embodiment, this invention provides a compound of formula IXA, where R₁-R₄ are defined as for formula I, and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, 2-pyrrolidon-1-yl, or 2-pyrrolidon-6-yl.

In a still more specific embodiment, this invention provides a compound of formula IXA, where R₁-R₃ are as defined for formula I, R₄ is H or methyl, and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl.

In a still more specific and more preferred embodiment, this invention provides a compound of formula IXA, where R₁ and R₂, in positions 2 and 6, are alkyl or halo, R₃ is H, R₄ is H or methyl, and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl.

In another more specific embodiment, this invention provides a compound of formula IXA, where R₁-R₄ are defined as for formula II, and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula IXA, where R₁-R₃ are as defined for formula II, R₄ is H or methyl, and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific and more preferred embodiment, this invention provides a compound of formula IXA, where R₁ and R₂, in positions 2 and 6, are alkyl or halo, R₃ is alkyl, haloalkyl, cycloalkyl, alkenyl, or alkynyl, R₄ is H or methyl, and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific and more preferred embodiment, this invention provides a compound of formula IXA, where R₁ and R₂, in positions 2 and 6, are alkyl or halo, R₃ is H, R₄ is H or methyl, and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula IXA, where R₁ and R₂ are, independently, H, halo, or C₁-C₃ alkyl; R₃ and R₄ are both H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a preferred and more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-halo or 2-methyl; R₂ is 6-methyl; R₃ and R₄ are, independently, H, C₁-C₃ alkyl, or halo; and R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-chloro; R₂ is 6-methyl; R₃ and R₄ are, independently, H, C₁-C₃ alkyl, vinyl, cyclopropyl, or halo; and R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-methyl; R₂ and R₃ are H; R₄ is methyl; and R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides a compound of formula IXA, in which R₁-R₄ are H; and R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred subgeneric embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-chloro; R₂ is 6-methyl; R₃ and R₄ are, independently, H, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ alkenyl, C₁-C₃ alkenoxy, hydroxy, or halo; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-chloro; R₂ is 6-methyl; R₃ and R₄ are, independently, H, methyl, methoxy, vinyl, 2-methoxyethene, hydroxy, or chloro; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, where R₁ is C₂-C₆ alkenyl, C₂-C₆ alkynyl, or C₁-C₆ cycloalkyl; R₂ and R₃ are H; R₄ is H or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula IXA, where R₁ is 2-methylpropenyl, 1-propynyl, or cyclopropyl; R₂ and R₃ are H; R₄ is H or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, where R₁ is amino, methyl amino, dimethylamino, dimethylaminomethyl, or acetamido; R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, where R₁ is nitro, cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl; R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, where R₁ is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl; R₂-R₄ are H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-methyl; R₂ and R₃ are both halogen; R₄ is H; R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂ are both chloro; R₃ is H; R₄ is methyl; R′ is —(CH₂)_(n)-G, where n is 1, and G is piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, or tetrahydro furyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 3-methyl; R₂ and R₃ are both H; R₄ is 2-chloroethyl; R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-hydroxymethyl; R₃ is 4-CF₃; R₂ and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which R₁ 3-methyl; R₂ is 5-chloro; R₃ and R₄ are both H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another specific embodiment, this invention provides a compound of formula IXA, in which one or both of R₁ and R₂ are CF₃; R₃ and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1, and G is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In another subgeneric embodiment, this invention provides a compound of formula IXA, in which R₁ is isothiazolyl, isoxazolyl, oxazolyl, oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl; R₂, R₃, and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, pyrimidinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl; oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolyl, isothiazolinyl, isothiazolidinyl, isothiazolidinonyl, indolyl, indolyl, oxindolyl, isoindolyl, quinolyl, isoquinolyl, or naphthyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 3-chloro; R₂, R₃, and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 2-chloro; R₂ is 6-methyl; R₃; and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 4-chloro; R₂, R₃, and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ and R₂ are 2- and 6-chloro; R₂, R₃, and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 2-bromo; R₂; R₃; and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 3-bromo; R₂; R₃; and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 4-bromo; R₂, R₃, and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 2-, 3-, or 4-bromo; R₂, R₃, and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1, and G is R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 4-bromo; R₂ is 2-methyl; R₃ is 3-methyl; R₄ is H, methyl, or halo; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 2-bromo; R₂ is 6-methyl; R₃ is 3-methyl; R₄ is H, methyl, or halo; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 3-bromo; R₂ is 6-methyl; R₃ is H; R₄ is H, methyl, or halo; and R′ is C₁-C₄ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 2-chloro; R₂ is 4-chloro; R₃ and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 2-methyl; R₂ is 6-methyl; R₃ and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which one or both of R₁ and R₂ are CF₃; R₃ and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-CF₃; R₂; R₃; and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂, in positions 2 and 6, are, independently, methyl or halogen; R₃ is 2-chloromethyl, R₄ is H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-piperidyl, 3-piperidyl, or 4-piperidyl or R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂, in positions 2 and 6, are, independently, methyl or halogen; R₃ is 3-fluoromethyl; and R₄ is H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 2-pyrimidyl, 4-pyrimidyl, 2-morpholyl, or 3-morpholyl or R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂, in positions 2 and 6, are, independently, methyl or halogen; R₃ is 3-methyl; and R₄ is H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-piperidyl, 3-piperidyl, or 4-piperidyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂, in positions 2 and 6, are, independently, methyl or halogen; R₃ is 3-fluoromethyl; and R₄ is H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-bromo-2-pyrimidyl, 2-chloro-4-pyrimidyl, 2-morpholyl, or 3-morpholyl.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 3-cyano; R₂ is H or 6-methyl; R₃ and R₄ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 3-hydroxy; R₂ is H or 6-methyl; R₃ and R₄ are, independently, H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 4-hydroxy; R₂ is H or 2-methyl; R₃ and R₄ are, independently, H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-, 3-, or 4-methoxy; R₂ is H or 2-methyl; R₃ and R₄ are, independently, H, hydroxy, or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-, 3-, or 4-methoxy; R₂ is H or 6-methyl; R₃ and R₄ are, independently, H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-, 3-, or 4-ethoxymethyl; R₂ is H or 6-methyl; R₃ and R₄ are, independently, H, hydroxy, or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-, 3-, or 4-methoxymethyl; R₂ is H or 6-methyl; R₃ and R₄ are, independently, H, hydroxy, methoxy, halo, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 3-(2-methoxyethyl); R₂ is H, 2-methyl, or 6-methyl; R₃ and R₄ are, independently, H, hydroxy, methoxy, or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 4-(2-methoxyethyl); R₂ is H, 2-methyl, or 6-methyl; R₃ and R₄ are, independently, H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3-, or 4-dimethylamino; R₂ is H or 6-methyl; R₃ and R₄ are, independently, H, methyl, or hydroxy; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3-, or 4-dimethylamino; R₂ is H or 6-methyl; R₃ is 3-methyl; R₄ is methyl, halo, or H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3-, or 4-dimethylaminocarbonyl; R₂ is H or 6-methyl; R₃ is H or methyl; R₄ is H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3-, or 4-methyloxycarbonyl; R₂ is H or 6-methyl; R₃ is H or methyl, R₄ is H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3-, or 4-acetyl; R₂ is H or 6-methyl, R₃ is H, chloro, or methyl; R₄ is H or 5-methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3-, or 4-acetoxy; R₂ is H or 6-methyl; R₃ is H or methyl; R₄ is H, methyl, or chloro; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3-, or 4-dimethylamino; R₂ is H or 6-methyl; R₃ is H or methyl; R₄ is H, methyl, hydroxy, methoxy, or chloro; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3- or 4-dimethylaminocarbonyl; R₂ is H or 6-methyl; R₃ is H or 3-methyl; R₄ is H, methyl, or chloro; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3-, or 4-methyloxycarbonyl; R₂ is H or 6-methyl; R₃ is H or methyl; R₄ is H, methyl, hydroxy, methoxy, or chloro; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3- or 4-chloroacetyl; R₂ is H or 6-methyl; R₃ is H or methyl; R₄ is H, methyl, hydroxy, methoxy, or chloro; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3- or 4-acetoxy; R₂ is H or 6-methyl; R₃ is H or methyl; R₄ is H, hydroxy, methoxy, or chloro; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3- or 4-fluoromethyl; R₂ is H or 6-methyl; R₃ is H or methyl; R₄ is H or 5-chloro; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 4-cyano; R₂ is H or 6-methyl; R₃ is H or methyl; R₄ is H, methyl, hydroxy, methoxy, halomethyl, or chloro; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups, or R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-, 3- or 4-ethoxy; R₂ is H or 6-methyl; R₃ is H or methyl; R₄ is H, methyl, hydroxy, methoxy, vinyl, halomethyl, or chloro; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-, 3-, or 4-vinyl; R₂ is H or 6-methyl; R₃ is H or methyl; R₄ is H, methyl, or chloro; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-, 3-, or 4-chloromethoxy; R₂ is H or 6-methyl; R₃ is H or methyl; R₄ is H, methyl, hydroxy, methoxy, or chloro; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 4-methoxy; R₂-R₄ are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-methyl; R₂ is 4-methylsulfonyl; R₃ and R₄ are, independently, H, hydroxy, halomethyl, or methyl; and R′ is —(CH₂)_(r)-G, where n is 1, and G is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-, 3-, or 4-methoxy; R₂ is H or 6-methyl; R₃ is H or methyl; R₄ is H, methyl, or chloro; and R′ is —(CH₂)_(n)-G, where n is 1, and G is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-, 3-, or 4-bromo; R₂ is H or 6-methyl; R₃ is H or methyl; R₄ is H, methyl, or chloro; and R′ is —(CH₂)_(n)-G, where n is 1, and G is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-chloro; R₂ is 3-, 4-, 5-, or 6-cyclopropyl, R₃ and R₄ are, independently, H, halo, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 3-cyclopropyl; R₂-R₄ are H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 3-cyclopropyl; R₂ is 2-, 4-, 5-, or 6-chloro; R₃ and R₄ are H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-chloro; R₂ is trans-4-(2-methylcyclopropyl); R₃ and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 1, and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 4-cyclopropyl; R₂ is 2- or 3-chloro; R₃ and R₄ are, independently, H, halo, or C₁-C₃ alkyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 4-isopropyl; R₂ is 2-chloro; R₃ is 2- or 3-chloro; R₄ is methyl, hydroxy, methoxy, or halo; and R′ is —(CH₂)_(n)-G, where n is 1, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂ are both halogen; R₃ is 3-methyl; R₄ is H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂ are both H; R₃ is 3-chloro; R₄ is methyl, hydroxy, methoxy, or halo; and R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂ are both H; R₃ is 2-(2-chloroethyl); R₄ is methyl, hydroxy, methoxy, or halo; R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-hydroxymethyl; R₂ is 4-CF₃; R₃ and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 3-chloro; R₂ and R₃ are both H; R₄ is methyl; and R′ is —(CH₂)_(n)-G, where n is 2, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula IXA, in which one or both of R₁ and R₂ are CF₃; R₃ and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 4-chloro; R₂ is 3-chloro; R₃ and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 2-, 3-, or 4-fluoro; R₂, R₃, and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is fluoro; R₂ is methyl; R₃ and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 6-chloro; R₂, R₃, and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 2-bromo, 3-bromo, or 4-bromo; R₂ is methyl; R₃; and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 2-(2-chloroethyl); R₂ is 6-chloro; R₃ and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula IXA, in which R₁ is 4-(3-chloropropyl); R₂ is 2-bromomethyl; R₃ and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-CF₃; R₂, R₃, and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is isothiazol-4-yl, isoxazol-4-yl, oxazol-2-yl, 2-oxazolin-4-yl, oxazolidin-5-yl, or thiazol-2-yl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 4-cyano; R₂ is 2-methyl; R₃ and R₄ are H or methyl; R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-methyl; R₂ is 4- or 5-hydroxy; R₃ and R₄ are, independently, H, hydroxy, methoxy, halo, or methyl; R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-hydroxymethyl; R₂-R₄ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-methoxy; R₂ is H, halo, or methyl; R₃ and R₄ are, independently, H or methyl; R′ is —(CH₂)_(n)-G, where n is 2, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 4-methoxy; R₂-R₄ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3-, or 4-dimethylamino; R₂; R₃; and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3-, or 4-acetyl; R₂, R₃, and R₄ are H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3-, or 4-acetoxy; R₂, R₃, and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 4-methyloxycarbonyl; R₂ is H or methyl; R₃ and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3-, or 4-acetyl; R₂, R₃, and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3-, or 4-acetoxy; R₂; R₃; and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention contemplates a compound of formula IXA, in which R₁ is 2-, 3-, or 4-CH₂F; R₂; R₃; and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-, 3-, or 4-cyano; R₂-R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-, 3-, or 4-ethoxy; R₂-R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-, 3-, or 4-trifluoromethoxy; R₂-R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-, 3-, or 4-chloromethoxy; R₂-R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, morpholyl, or imidazolyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-, 3-, or 4-methoxy; R₂-R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is 5-oxazolidinyl, 4-thiazolyl, 3-thienyl, 2-furyl, 3-pyrrolyl, 2-pyrrolidinyl, N-pyrrolidinonyl, N-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 3- or 4-methylsulfonyl R₂ is 2-(2-methyl cyclopropyl); R₃ and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, N-pyrrolidonyl, or m-tolyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2-, 3-, or 4-methoxy; R₂-R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 4-bromo or 4-bromomethyl; R₂-R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2- or 3-chloro; R₂ is 4-(2-cyclopropylethyl); R₃ and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is cyclopropyl or cyclopropylmethyl; R₂-R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is trans-3-(2-methylcyclopropyl); R₂ is 6-chloro; R₃ and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 3- or 4-cyclopropyl; R₂ is 5-chloro; R₃ is 2-(2-fluoroethyl); and R₄ is H, hydroxy, methoxy, or halo; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is 2- or 3-cyclopropyl; R₂ is 6-chloro; R₃ is 3-chloro; R₄ is methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In another embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂ are halogen or methyl; R₃ and R₄ are H; and R′ is methyl, ethyl, isopropyl, or sec-butyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is halogen or methyl; R₂-R₄ are H; and R′ is methyl, ethyl, isopropyl, or sec-butyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂ are, independently, halogen or methyl; R₃ and R₄ are H; and R′ is 1,2-chloropropan-3-yl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂ are, independently, halogen or methyl; R₃ and R₄ are H; and R′ is 1-hydroxy-butan-3-yl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ is bromo; R₂-R₄ are H; and R′ is isopropyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂ are, independently, halogen or methyl; R₃ and R₄ are H; and R′ is 1,2-dihydroxy-propan-3-yl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂ are, independently, halogen or methyl; R₃ and R₄ are H; and R′ is 2-hydroxyethyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂ are, independently, halogen or methyl; R₃ and R₄ are H; and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂ are, independently, halogen or methyl; R₃ and R₄ are H; and R′ is 1,2-dihydroxybutan-4-yl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂ are, independently, halogen or methyl; R₃ and R₄ are C₁-C₆ alkyl; and R′ is 1,2-dihydroxybutan-3-yl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂ are halogen or methyl; R₃ and R₄ are H; and R′ is 4-methoxybutyl.

In another more specific embodiment, this invention provides a compound of formula IXA, in which R₁ and R₂ are, independently, halogen or methyl; R₃ and R₄ are H; and R′ is 3-hydroxypropyl.

In another more specific embodiment, this invention provides a compound of formula IXA, where R₁ and R₂ together are fused cyclohexyl or fused cyclopentyl; R₃ and R₄ are H; and R′ is isopropyl, (2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula IXA, where R₁ and R₂, at positions 3 and 4, are fused (4,5)-imidazolo; R₃ and R₄ are H; and R′ is isopropyl, (2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-Butyl.

In another more specific embodiment, this invention contemplates a compound of formula IXA, where R₁ and R₂, at positions 3 and 4, are fused (2,3)-furyl; R₃ and R₄ are H; and R′ is isopropyl, (2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula IXA, where R₁ and R₂, at positions 3 and 4, are fused (2,3)-pyrido; R₃ and R₄ are H; and R′ is isopropyl, (2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula IXA, where R₁ and R₂, at positions 3 and 4, are fused (3,4)pyrrolyl; R₃ and R₄ are H; and R′ is isopropyl, (2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula IXA, where R₁ and R₂, at positions 2 and 3, are fused cyclopentyl; R₃ and R₄ are H; and R′ is isopropyl, (2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula IXA, where R₁ and R₂, at positions 3 and 4, are fused cyclopentyl; R₃ and R₄ are H; and R′ is isopropyl, (2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula IXA, where R₁ and R₂, at positions 2 and 3, are benzo; R₃ and R₄ are H; and R′ is isopropyl, (2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula IXA, where R₁ and R₂, at positions 2 and 3, are benzo, substituted at one or both ortho positions; R₃ and R₄ are H; and R′ is isopropyl, (2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula IXA, where R₁ and R₂, at positions 3 and 4, are benzo; R₃ and R₄ are H; and R′ is isopropyl, (2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl. Specific prophetic examples of compounds of formula IXA are shown below,

Subgeneric embodiments of formula IXB are shown below:

In one subgeneric embodiment, this invention provides a compound of any of formulas IXB-1-IXB-6, in which R₁, R₂, and R₄ are, independently, H, C₁-C₄ alkyl, alkenyl, alkynyl, cycloalkyl, cyano, acetyl, acetoxy, acetamido, methylcarbamoyl, dimethylamino, or halo; R₃ is H, and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, optionally substituted as described above, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a more specific embodiment, this invention provides a compound according to formula IXB-1, where R₁ is 3-methyl or 3-halo; R₂ and R₃ are H; R₄ is H, vinyl, cyano, halo, hydroxy, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a more specific embodiment, this invention provides a compound according to formula IXB-1, where R₁ is 3-methyl or 3-halo; R₂ and R₃ are H; R₄ is H or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound according to formula IXB-2, where R₁ is 2-methyl or 2-halo; R₂ and R₃ are, independently, H, halo, C₁-C₆ alkyl, or C₁-C₆ alkenyl, said alkyl and alkenyl groups optionally substituted as described above; R₄ is H, vinyl, cyano, halo, hydroxy, or C₁-C₆ alkyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound according to formula IXB-2, where R₁ is 4-methyl or 4-halo; R₂ and R₃ are H; R₄ is H, OH, halo, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups or R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound according to formula IXB-2, where R₁ is 2-methyl; R₂ is 4-halo; R₃ is H; R₄ is H, OH, halo, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound according to formula IXB-2, where R₁ is 2-halo; R₂ is 4-methyl; R₃ is H; R₄ is H, OH, halo, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound according to formula IXB-2, where R₁ is 2-methyl; R₂ is 4-chloro; R₃ is H; R₄ is H, OH, or methyl; and R′ is isopropyl, (2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound according to formula IXB-2, where R₁ is 2-chloro; R₂ is 4-methyl; R₃ is H; R₄ is H, OH, or methyl; and R′ is isopropyl, (2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound according to formula IXB-3, where R₁ is 4-methyl or 4-halo; R₂ and R₃ are H; R₄ is H, vinyl, cyano, halo, hydroxy, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound according to formula IXB-3, where R₁ is 4-methyl or 4-halo; R₂ is 6-methyl or 6-halo; R₃ is H; R₄ is H, hydroxy, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound according to formula IXB-3, where R₁ is 4-methyl or 4-halo; R₂ is 6-methyl or 6-halo; R₃ is H; R₄ is H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In another more specific embodiment, this invention provides a compound according to formula IXB-3, where R₁ is 4-methyl or 4-halo; R₂ is 6-methyl or 6-halo; R₃ is H; R₄ is H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound according to formula IXB-3, where R₁ is 4-methyl or 4-halo; R₂ is H, 6-methyl, or 6-halo; R₃ is H, C₁-C₃ alkyl, dimethylamino methyl; chloromethyl, or bromomethyl; R₄ is H or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups or R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound according to formula IXB-3, where R₁ is 4-methyl; R₂ is 6-chloro; R₃ is H; R₄ is H, OH, or methyl; and R′ is isopropyl, 1-hydroxy-2-propyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl, or R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound according to formula IXB-3, where R₁ is 4-chloro; R₂ is 6-methyl; R₃ is H; R₄ is H, OH, or methyl; and R′ is isopropyl, 1-hydroxy-2-propyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl, or R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound according to formula IXB-4, where R₁ is 5-methyl or 4-halo; R₂ is 6-methyl or 6-halo; R₃ is H; 4 is H, hydroxy, halo, C₁-C₆ alkyl, or C₁-C₆ alkenyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups, or R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound according to formula IXB-4, where R₁ is 5-methyl; R₂ is H, 6-methyl, or 6-chloro; R₃ is H; R₄ is H, OH, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups, or R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound according to formula IXB-4, where R₁ and R₂, at positions 5 and 6, are fused benzo or pyrido; R₃ is H; R₄ is H, OH, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups, or R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound according to formula IXB-4, where R₁ is 5-chloro; R₂ is H, 6-methyl, or 6-chloro; R₃ is H; R₄ is H, OH, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups, or R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or 4-imidazolyl.

In a more specific embodiment, this invention provides a compound according to formula IXB-5, where R₁ is 3-(C₁-C₄ alkyl), 3-(C₁-C₄ alkenyl), or 3-halo; R₂ and R₃ are H; R₄ is H, vinyl, cyano, halo, hydroxy, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups, or R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or 4-imidazolyl.

In a more specific embodiment, this invention provides a compound according to formula IXB-5, where R₁ is 3-methyl or 3-halo; R₂ is 5-methyl or 5-halo; R₃ is H; R₄ is H, OH, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups, or R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or 4-imidazolyl or R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In a still more specific embodiment, this invention provides a compound according to formula IXB-5, where R₁ is 3-methyl; R₂ is 5-chloro; R₃ is H; R₄ is H, OH, or methyl; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In a still more specific embodiment, this invention provides a compound according to formula IXB-5, where R₁ and R₂, at positions 2 and 3, are fused benzo, pyrido, pyrrolo, or imidazolo, optionally substituted with halogen, methyl, halomethyl, or hydroxy; R₃ is H; R₄ is H, OH, or methyl; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In a still more specific embodiment, this invention provides a compound according to formula IXB-5, where R₁ is 3-methyl; R₂ is 5-chloro; R₃ is H; R₄ is H, OH, or methyl; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound according to formula IXB-5, where R₁ is H, 2-methyl, 2-nitro, 2-methylcarbamoyl, or 2-halo; R₂ is 3-methyl or 3-chloro, and R₃ is H, 5-methyl, or 5-chloro; R₄ is H, OH, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups or R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or 4-imidazolyl or R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound according to formula IXB-5, where R₁ is H, 2-acetyl, 2-acetamido, 2-dimethylamino, or 2-halomethyl; R₂ is 3-methyl or 3-chloro, and R₃ is H, 5-methyl, or 5-chloro; R₄ is H or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another still more specific embodiment, this invention provides a compound according to formula IXB-5, where R₁ is 3-methyl; R₂ is H or 5-chloro; R₃ is H; R₄ is H; and R′ is isopropyl, 1-hydroxy-2-propyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound according to formula IXB-5, where R₁ is H, 2-bromomethyl, 2-ethynyl, 2-cyano; R₂ is 3-chloro; R₃ is H or 5-methyl; R₄ is H or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound according to formula IXB-5, where R₁ is H or 2-chloro; R₂ is 3-chloro; R₃ is H or 5-chloro; R₄ is H or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound according to formula IXB-5, where R₁ is H or 2-chloro; R₂ is 3-chloro; R₃ is H or 5-chloro; R₄ is H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound according to formula IXB-6, where R₁ is H, 4-acetyl, 4-acetamido, 4-dimethylamino, 4-C₁-C₄ alkyl, alkenyl, alkynyl, or cycloalkyl, or 4-halomethyl; R₂ is H, 5-methyl or 5-halo, and R₃ is H, 6-methyl, or 6-chloro; R₄ is H, hydroxy, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound according to formula IXB-6, where R₁ is 4-methyl; R₂ is H or 5-chloro; R₃ is H or 6-chloro; R₄ is H or methyl; and R′ is isopropyl, 1-hydroxy-2-propyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound according to formula IXB-6, where R₁ is H, 4-bromomethyl, 4-ethynyl, 4-cyano; R₂ is H, 5-methyl, or 5-chloro; R₃ is H, 6-acetyl, 6-acetoxy, 6-acetamido, or 6-methylcarbamoyl; R₄ is H, vinyl, chloromethyl, hydroxy, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound according to formula IXB-6, where R₁ and R₂, at positions 4 and 5, are fused benzo; R₃ is H or 6-methyl; R₄ is H, halo, halomethyl, hydroxy, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups or R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl, or R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound according to formula IXB-6, where R₁ and R₂, at positions 4 and 5, are (2,3) fused imidazolo, pyrido, or pyrrolo; R₃ is H or 6-methyl; R₄ is H, halo, halomethyl, or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

Prophetic examples of additional compounds of formula IXB are shown below

In another generic embodiment, this invention provides a compound of formula X

where M, Q, T, U, V, W, X, Y, and Z represent N, CH, or CR_(1, 2, 3, or 4), where R₁-R₄ are defined as for formula I.

In a subgeneric embodiment, this invention provides a compound of formula XA where M, Q, T, U, V, W, X, Y, and Z are all CH or CR_(1, 2, 3, or 4). In another subgeneric embodiment, this invention provides a compound of formula XB,

where all substituents are as defined for formula I, and where at least one of M, Q, T, U, V, W, X, Y, and Z is N, provided that no ring contains 2 adjacent nitrogen atoms.

In one subgeneric embodiment, this invention provides a compound of formula XA, where R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolinyl, isothiazolidinyl, isothiazolidinonyl, imidazolinyl, imidazolyl, imidazolinonyl, pyridyl, pyrazyl, pyranyl, pyridazolyl, piperidinonyl, morpholyl, 2,6-dimethyl morpholyl, tetrahydrofuryl, piperazinyl, 1-methyl-piperazin-4-yl, piperazinonyl, 2-pyrrolidonyl, tolyl, phenyl, piperidinyl, pyrimidinyl, pyrazolyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, isoxazolidinonyl, isothiazolinyl, isothiazolidinyl, indolyl, oxindolyl, isoindolyl, quinolyl, isoquinolyl, or naphthyl.

In another preferred embodiment, this invention provides a compound of formula XA, where R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl.

In another preferred embodiment, this invention provides a compound of formula XA, where R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another preferred embodiment, this invention provides a compound of formula XA, where R₁ and R₂ are both ortho substituents.

In another preferred embodiment, this invention provides a compound of formula XA, where R₄ and R₅ occupy the 3- and 5-positions.

In a more specific embodiment, this invention provides a compound of formula XA, where R₁ and R₂ are as defined for formula I; R₄ and R₅ are both H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, where R₁ and R₂ are defined as in formula XA; R₄ and R₅ are both H; and R′ is C₁-C₆ alkyl or O—C₁-C₆ alkyl, both optionally substituted as described above.

In a still more specific embodiment, this invention provides a compound of formula XA, where R₁ and R₂ are H, halo, or C₁-C₃ alkyl; R₄ and R₅ are both H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a preferred and more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-halo; R₂ is 6-methyl; R₄ and R₅ are, independently, H, C₁-C₃ alkyl, or halo; and R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-chloro; R₂ is 6-methyl; R₄ and R₅ are, independently, H, C₁-C₃ alkyl, or halo; and R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are H; R₄ and R₅ are, independently, methyl or halo; and R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are H; R₄ and R₅ are, independently, methyl or chloro; and R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are H; R₄ and R₅ are 3-chloro and 5-methyl; and R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are H; R₅ is 2-chloro or 3-chloro; R₄ is H; and R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are H; R₅ is 2-methyl or 3-methyl; R₄ is H; and R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred subgeneric embodiment, this invention provides a compound of formula XA, in which R₁ is 2-chloro; R₂ is 6-methyl; R₄ and R₅ are, independently, H, C₁-C₃ alkyl, or halo; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, where R₁ is C₂-C₆ alkenyl, C₂-C₆ alkynyl, or C₁-C₆ cycloalkyl; R₂-R₅ are H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, where R₁ is amino, methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino; R₂-R₅ are H and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, where R₁ is nitro, cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl; R₂-R₅ are H and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, where R₁ is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl; R₂-R₅ are H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are both halogen; R₅ is 2-methyl; and R₄ is H; R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are both H; R₅ is 2-chloro; R₄ is 3-methyl; R′ is —(CH₂)_(n)-G, where n is 1, and G is piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, or tetrahydrofuryl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are both H; R₅ is 3-methyl; R₄ is 6-(2-chloroethyl); R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-hydroxymethyl; R₅ is 4-CF₃; R₂ and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are both H; R₅ is 3-methyl; R₄ is 5-chloro; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another specific embodiment, this invention provides a compound of formula XA, in which one or both of R₁ and R₂ are CF₃; R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1, and G is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In another subgeneric embodiment, this invention provides a compound of formula XA, in which R₁ is isothiazolyl, isoxazolyl, oxazolyl, oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl; R₂; R₄; and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, pyrimidinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl; oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolyl, isothiazolinyl, isothiazolidinyl, isothiazolidinonyl, indolyl, indolyl, oxindolyl, isoindolyl, quinolyl, isoquinolyl, or naphthyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 3-chloro; R₂; R₄ and R₅ are H; R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 2-chloro; R₂ is 6-methyl; R₄ and R₅ are H; R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 4-chloro; R₂; R₄ and R₅ are H; R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ and R₂ are 2,6-di-chloro; R₂; R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl; piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 2-bromo; R₂; R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 3-bromo; R₂; R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 4-bromo; R₂; R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 2-, 3-, or 4-bromo; R₂; R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1, and G is R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 4-bromo; R₂ is 2-methyl; R₅ is 3-methyl; R₄ is H, 5-methyl, or 5-halo; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 2-bromo; R₂ is 6-methyl; R₅ is 3-methyl; R₄ is H, 5-methyl, or 5-halo; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 3-bromo; R₂ is 6-methyl; R₅ is 3-methyl; R₄ is H, 5-methyl, or 5-halo; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 2-chloro; R₂ is 4-chloro; R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 2-methyl; R₂ is 6-methyl; R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula XA, in which one or both of R₁ and R₂ are CF₃; R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-CF₃; R₂; R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂, in positions 2 and 6, are methyl or halogen; R₅ is 2-chloromethyl, 4 is H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-piperidyl, 3-piperidyl, or 4-piperidyl or R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂, in positions 2 and 6, are methyl or halogen; R₅ is 3-fluoromethyl; and R₄ is H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 2-pyrimidyl, 4-pyrimidyl, 2-morpholyl, or 3-morpholyl or R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂, in positions 2 and 6, are methyl or halogen; R₅ is 3-methyl; and R₄ is H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-piperidyl, 3-piperidyl, or 4-piperidyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂, in positions 2 and 6, are methyl or halogen; R₅ is 3-fluoromethyl; and R₄ is H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-bromo-2-pyrimidyl, 2-chloro-4-pyrimidyl, 2-morpholyl, or 3-morpholyl.

In a still more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 3-cyano; R₂ is H or 6-methyl; R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In a still more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 3-hydroxy; R₂ is H or 6-methyl; R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 4-hydroxy; R₂ is H or 2-methyl; R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In a still more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-, 3-, or 4-methoxy; R₂ is H or 2-methyl; R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In a still more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-, 3-, or 4-methoxy; R₂ is H or 2-methyl; R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-, 3-, or 4-ethoxymethyl; R₂ is H or 2-methyl; R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XA, in which R is 2-, 3-, or 4-methoxymethyl; R₂ is H or 2-methyl; R₄ and R₅ are H, halo, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 3-(2-methoxyethyl); R₂ is H, 2-methyl, or 6-methyl; R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 4-(2-methoxyethyl); R₂ is H, 2-methyl, or 6-methyl; R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3-, or 4-dimethylamino; R₂ is H or 6-methyl; R₄ and R₅ are H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3-, or 4-dimethylamino; R₂ is H or 6-methyl; R₅ is 3-methyl; R₄ are 5-methyl, 5-halo, or H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3-, or 4-dimethylaminocarbonyl; R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ is H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3-, or 4-methyloxycarbonyl; R₂ is H or 6-methyl; R₅ is H or 3-methyl, R₄ is H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3-, or 4-acetyl; R₂ is H or 6-methyl, R₅ is H, 3-chloro, or 3-methyl; R₄ is H or 5-methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3-, or 4-acetoxy; R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3-, or 4-dimethylamino; R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3- or 4-dimethylaminocarbonyl; R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3-, or 4-methyloxycarbonyl; R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3- or 4-chloroacetyl; R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3- or 4-acetoxy; R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3- or 4-fluoromethyl; R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 4-cyano; R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups, or R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-, 3- or 4-ethoxy; R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-, 3-, or 4-vinyl; R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-, 3-, or 4-chloromethoxy; R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 4-methoxy; R₂-R₅ are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-methyl; R₂ is 4-methylsulfonyl; R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1, and G is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-, 3-, or 4-methoxy; R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is —(CH₂)_(n)-G, where n is 1, and G is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-, 3-, or 4-bromo; R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is —(CH₂)_(n)-G, where n is 1, and G is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-chloro; R₂ is 3-, 4-, 5-, or 6-cyclopropyl, R and R₅ are H, halo, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 3-cyclopropyl; R₂-R₅ are H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 3-cyclopropyl; R₂ is 2-, 4-, 5-, or 6-chloro; R₄ and R₅ are H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-chloro; R₂ is trans-4-(2-methylcyclopropyl); R4 and R5 are H; R′ is —(CH₂)_(n)-G, where n is 1, and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 4-cyclopropyl; R₂ is 2- or 3-chloro; R₄ and R₅ are H, halo, or C₁-C₃ alkyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 4-isopropyl; R₂ is 2-chloro; R₅ is 2- or 3-chloro; R₄ is 5- or 6-methyl; and R′ is —(CH₂)_(n)-G, where n is 1, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are both halogen; R₅ is 3-methyl; R₄ is H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are both H; R₅ is 3-chloro; R₄ is 5-methyl; and R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are both H; R₅ is 2-(2-chloroethyl); 4 is 3-methyl; R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-hydroxymethyl; R₂ is 4-CF₃; R₄ and R₅ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are both H; R₅ is 3-chloro; R₄ is 5-methyl; and R′ is —(CH₂)_(n)-G, where n is 2, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XA, in which one or both of R₁ and R₂ are CF₃; R₄ and R₅ are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In another subgeneric embodiment, this invention provides a compound of formula XA, in which R₁ is isothiazolyl, isoxazolyl, oxazolyl, oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl; R₂; R₅; and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, pyrimidinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl; oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolyl, isothiazolinyl, isothiazolidinyl, isothiazolidinonyl, indolyl, indolyl, oxindolyl, isoindolyl, quinolyl, isoquinolyl, and naphthyl.

In a more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 4-chloro; R₅ is 3-chloro; R₂ and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 2-, 3-, or 4-fluoro; R₂, R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is fluoro; R₂ is methyl; R₄ and R₅ are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 6-chloro; R₂, R₄ and R₅ are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 2-bromo; R₂ is methyl; R5; and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 3-bromo; R₂; R₄ and R₅ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 4-bromo; R₂, R₄ and R₅ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 2-(2-chloroethyl); R₂ is 6-chloro; R₄ and R₅ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates the compound of formula XA, in which R₁ is 4-(3-chloropropyl); R₂ is 2-bromomethyl; R₄ and R₅ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-CF₃; R₂, R₄ and R₅ are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is isothiazol-4-yl, isoxazol-4-yl, oxazol-2-yl, 2-oxazolin-4-yl, oxazolidin-5-yl, or thiazol-2-yl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 4-cyano; R₂ is 2-methyl; R₄ and R₅ are H or methyl; R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-methyl; R₂ is 4- or 5-hydroxy; R₄ and R₅ are H or methyl; R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-hydroxymethyl; R₂-R₅ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-methoxy; R₂ is H, halo, or methyl; R₄ and R₅ are H or methyl; R′ is —(CH₂)_(n)-G, where n is 2, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 4-methoxy; R₂-R₅ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3-, or 4-dimethylamino; R₂, R₄, and R₅ are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3-, or 4-dimethylaminocarbonyl; R₂ is H or 6-methyl, R₄ and R₅ are H, halo, or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3-, or 4-methyloxycarbonyl; R₂ is H, 6-methyl, or 6-halo; R₄ and R₅ are H, halo, or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl, or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3-, or 4-acetyl; R₂, R₄, and R₅ are H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3-, or 4-acetoxy; R₂, R₄, and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 2, and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 4-dimethylamino; R₂ is 2-methyl; R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 4-dimethylaminocarbonyl; R₂ is 2-methyl; R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 4-methyloxycarbonyl; R₂ is H or methyl; R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3-, or 4-acetyl; R₂, R₄, and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3-, or 4-acetoxy; R₂; R₅; and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention contemplates a compound of formula XA, in which R₁ is 2-, 3-, or 4-CH₂F; R₂; R₄; and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-, 3-, or 4-cyano; R₂-R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-, 3-, or 4-ethoxy; R₂-R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-, 3-, or 4-trifluoromethoxy; R₂-R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-, 3-, or 4-chloromethoxy; R₂-R₅ are H; and R′ is —(CH₂)_(n)-(G, where n is 1 or 2, and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, morpholyl, or imidazolyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-, 3-, or 4-methoxy; R₂-R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is 5-oxazolidinyl, 4-thiazolyl, 3-thienyl, 2-furyl, 3-pyrrolyl, 2-pyrrolidinyl, N-pyrrolidinonyl, N-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 3- or 4-methylsulfonyl R₂ is 2-(2-methyl cyclopropyl); R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, N-pyrrolidonyl, or m-tolyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2-, 3-, or 4-methoxy; R₂-R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 4-bromo or 4-bromomethyl; R₂-R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2- or 3-chloro; R₂ is 4-(2-cyclopropylethyl); R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is cyclopropyl or cyclopropylmethyl; R₂-R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is trans-3-(2-methylcyclopropyl); R₂ is 6-chloro; R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 3- or 4-cyclopropyl; R₂ is 5-chloro; R₅ is 2-(2-fluoroethyl); and R₄ is H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is 2- or 3-cyclopropyl; R₂ is 6-chloro; R₅ is 3-chloro; R₄ is 5-methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In another embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ are H; and R′ is methyl, ethyl, isopropyl, or sec-butyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is halogen or methyl; R₂-R₅ are H; and R′ is methyl, ethyl, isopropyl, or sec-butyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ are H; and R′ is 1,2-chloropropan-3-yl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ are H; and R′ is 1-hydroxy-butan-3-yl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ is bromo; R₂-R₅ are H; and R′ is isopropyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ are H; and R′ is 1,2-dihydroxy-propan-3-yl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ are H; and R′ is 2-hydroxyethyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ are H; and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ are H; and R′ is 1,2-dihydroxybutan-4-yl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ are C₁-C₆ alkyl; and R′ is 1,2-dihydroxybutan-3-yl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ are H; and R′ is 4-methoxybutyl.

In another more specific embodiment, this invention provides a compound of formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ are H; and R′ is 3-hydroxypropyl.

In another more specific embodiment, this invention provides a compound of formula XA, where R₁ and R₂ are fused cyclohexyl or fused cyclopentyl; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula XA, where R₁ and R₂, at positions 3 and 4, are fused (4,5)-imidazolo; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-Butyl.

In another more specific embodiment, this invention contemplates a compound of formula XA, where R₁ and R₂, at positions 3 and 4, are fused (2,3)-furyl; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula XA, where R₁ and R₂, at positions 3 and 4, are fused (2,3)-pyrido; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula XA, where R₁ and R₂, at positions 3 and 4, are fused (3,4)pyrrolyl; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula XA, where R₁ and R₂, at positions 2 and 3, are fused cyclopentyl; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula XA, where R₁ and R₂, at positions 3 and 4, are fused cyclopentyl; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula XA, where R₁ and R₂, at positions 2 and 3, are benzo; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula XA, where R₁ and R₂, at positions 2 and 3, are benzo, substituted at one or both ortho positions; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula XA, where R₁ and R₂, at positions 3 and 4, are benzo; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl. The prophetic examples below show specific embodiments of this invention.

In additional subgeneric embodiments, this invention provides aza-substituted compounds of the types shown below, where substituents R₁-R′ are as defined above.

In one more specific embodiment, this invention provides a compound of formula XB1, where R₁-R₅ are, independently, H, methyl, halo, nitro, cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB2, where R₁-R₅ are, independently, H, methyl, halo, nitro, cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB3, where R₁-R₅ are, independently, H, methyl, halo, nitro, cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB4, where R₁-R₅ are, independently, H, methyl, halo, nitro, cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB5, where R₁-R₅ are, independently, H, methyl, halo, nitro, cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB6, where R₁-R₅ are, independently, H, methyl, halo, nitro, cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB7, where R₁-R₅ are, independently, H, methyl, halo, nitro, cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB8, where R₁-R₅ are, independently, H, methyl, halo, nitro, cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB9, where R₁-R₄ are, independently, H, methyl, halo, nitro, cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB10, where R₁-R₅ are, independently, H, methyl, halo, nitro, cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In one more specific embodiment, this invention provides a compound of formula XB11, where R₁-R₅ are, independently, H, methyl, halo, nitro, cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In one more specific embodiment, this invention provides a compound of formula XB12, where R₁-R₅ are, independently, H, methyl, halo, nitro, cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB1, where R₁-R₅ are, independently, H, methyl, halo, acetyl, acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB2, where R₁-R₅ are, independently, H, methyl, halo, acetyl, acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB3, where R₁-R₅ are, independently, H, methyl, halo, acetyl, acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB4, where R₁-R₄ are, independently, H, methyl, halo, acetyl, acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB5, where R₁-R₅ are, independently, H, methyl, halo, nitro, cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB6, where R₁-R₅ are, independently, H, methyl, halo, acetyl, acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB7, where R₁-R₅ are, independently, H, methyl, halo, acetyl, acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB8, where R₁-R₅ are, independently, H, methyl, halo, acetyl, acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB9, where R₁-R₅ are, independently, H, methyl, halo, acetyl, acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB10, where R₁-R₅ are, independently, H, methyl, halo, acetyl, acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB11, where R₁-R₅ are, independently, H, methyl, halo, acetyl, acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB12, where R₁-R₅ are, independently, H, methyl, halo, acetyl, acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In one more specific embodiment, this invention provides a compound of formula XB1, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl, cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy, hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB2, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl, cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy, hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB3, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl, cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy, hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB4, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl, cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy, hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB5, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl, cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy, hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB6, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl, cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy, hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB7, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl, cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy, hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB8, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl, cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy, hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB9, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl, cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy, hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB10, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl, cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy, hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In one more specific embodiment, this invention provides a compound of formula XB11, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl, cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy, hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In one more specific embodiment, this invention provides a compound of formula XB12, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl, cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy, hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula XB1, where R₁-R₅ are, independently, H, halo, methyl, or halomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB2, where R₁-R₅ are, independently, H, halo, methyl, or halomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB3, where R₁-R₅ are, independently, H, halo, methyl, or halomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB4, where R₁-R₅ are, independently, H, halo, methyl, or halomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB5, where R₁-R₅ are, independently, H, halo, methyl, or halomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB6, where R₁-R₅ are, independently, H, halo, methyl, or halomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB7, where R₁-R₅ are, independently, H, halo, methyl, or halomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB8, where R₁-R₅ are, independently, H, halo, methyl, or halomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB9, where R₁-R₅ are, independently, H, halo, methyl, or halomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compound of formula XB10, where R₁-R₅ are, independently, H, halo, methyl, or halomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula XB111, where R₁-R₅ are, independently, H, halo, methyl, or halomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compound of formula XB12, where R₁-R₅ are, independently, H, halo, methyl, or halomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

Additional subgeneric embodiments are shown below.

In an even more specific and preferred embodiment, this invention provides a compound of formula XB1, where R₁-R₄ are, independently, H, chloro, or methyl, R₅ is H, and R′ is C₁-C₄ alkyl, optionally substituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this invention provides a compound of formula XB2, where R₁-R₅ are, independently, H, chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionally substituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this invention provides a compound of formula XB3, where R₁-R₅ are, independently, H, chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionally substituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this invention provides a compound of formula XB4, where R₁-R₅ are, independently, H, chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionally substituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this invention provides a compound of formula XB5, where R₁-R₅ are, independently, H, chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionally substituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this invention provides a compound of formula XB6, where R₁-R₅ are, independently, H, chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionally substituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this invention provides a compound of formula XB7, where R₁-R₅ are, independently, H, chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionally substituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this invention provides a compound of formula XB8, where R₁-R₅ are, independently, H, chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionally substituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this invention provides a compound of formula XB9, where R₁-R₅ are, independently, H, chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionally substituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this invention provides a compound of formula XB10, where R₁-R₅ are, independently, H, chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionally substituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this invention provides a compound of formula XB11, where R₁-R₅ are, independently, H, chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionally substituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this invention provides a compound of formula XB12, where R₁-R₅ are, independently, H, chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionally substituted with one or two or hydroxyl groups.

The prophetic examples below provide specific examples of subgeneric structures XB-1-XB-12.

In another generic embodiment, this invention provides a compound of formula XI below,

where the dashed bond represents an optional double bond, where symbols L, T, U, V, and W-Z represent N, CH, or CR_(1, 2, or 4), provided that no two nitrogen atoms are adjacent, where R₁-R₄ are, independently, hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₆ alkyl; O—C₁-C₆ alkyl; C₂-C₆ alkenyl; C₂-C₆ alkynyl; C₁-C₆ cycloalkyl; 2-methoxy ethenyl; CH₃OC(O); CH₃CH₂OC(O); C₁-C₅ alkyl-C(O)—; C₁-C₅ alkyl-C(O)O—; —NR₆R₇, —CH₂NR₆R₇, —NH—C(O)—R₆, —C(O)NR₈R₉; CH₃S(O)₂—, or —S(O)₂NR₈R₉, where R₆-R₉ are, independently, H or C₁-C₄ alkyl; or any of the pairs R₁ and R₂, R₆ and R₇, or R₈ and R₉, together with the ring atoms to which they are attached, form an additional, five- or six-membered ring, optionally containing one or two heteroatoms selected from O, N, and S, which ring may be aromatic or aliphatic, and which ring is fused in the case of R₁ and R₂; and where R₁ may also be isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, tolyl, or phenyl, wherein all alkyl, alkenyl, and cycloalkyl groups and all rings are optionally substituted with 1-3 halogen atoms, C₁-C₃ alkyl groups, or trifluoromethyl groups; R′ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; or R′ is —(CH₂)_(n)-G where n is 1 or 2 and G is a five- or six-membered ring or a 9- to 14-member fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds.

In one subgeneric embodiment, this invention provides a compound of formula XIA-1,

where R₁-R′ are as defined above for formula I.

In a more specific embodiment, this invention provides a compound of formula XIA-1, where R₁-R₄ are as described above for formula I, and where R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups, or R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is isothiazolyl, isoxazolyl, isoxazolidinyl, isoxazolidinonyl, oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolinyl, isothiazolidinyl, isothiazolidinonyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compound of formula XIA-1, where R₃ and R₄ are both H and R′ is C₁-C₆ alkyl or O—C₁-C₆ alkyl, both optionally substituted as described above.

In another more specific embodiment, this invention provides a compound of formula XIA-1, where R₂-R₅ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula XIA-1, where R₁ is amino, methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino, R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula XIA-1, where R₁ is nitro, cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl, R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ and R₂ are both halogen, R₃ is 2-methyl, and R₄ is H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a more specific embodiment, this invention contemplates a compound of formula XIA-1, where R₁-R₄ are H and R′ is 2-(2-furyl)ethyl, 2-hydroxyethyl, or 2,3-dihydroxy-1-propyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ and R₂ together, at positions 3 and 4, are fused cyclopentyl, R₃ and R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ and R₂ together, at positions 3 and 4, are benzo, R₃ and R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ and R₂ together, at positions 3 and 4, are 2,3-pyrido, R₃ and R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ and R₂ together, at positions 3 and 4, are 2,3-pyrrolo, R₃ and R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ and R₂ together, at positions 4 and 5, are fused (2,3)-furyl, R₃ and R₄ are H, and R′ is 1,2-dihydroxy-propan-3-yl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ and R₂ together, at positions 3 and 4, are fused (2,3)thienyl, R₃ and R₄ are H, and R′ is 2-hydroxyethyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is 2-chloro, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is 2-(2-chloroethyl), R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 4-CF₃, R₃ is 2-hydroxymethyl, R₂ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is 2-chloro, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which one or both of R₁ and R₂ are CF₃, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is isothiazolyl, isoxazolyl, oxazolyl, oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl; R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, pyrimidinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl; oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolyl, isothiazolinyl, isothiazolidinyl, isothiazolidinonyl, indolyl, indolyl, oxindolyl, isoindolyl, quinolyl, isoquinolyl, and naphthyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 2-chloro, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 3-chloro, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 4-chloro, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 5-chloro, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 3-bromo, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 4-bromo, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 5-bromo, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 2-chloro, R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 3-chloro, R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which one or both of R₁ and R₂ are CF₃, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-CF₃, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-cyano, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-hydroxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 4-hydroxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-methoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-dimethylamino, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-dimethylaminocarbonyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-methyloxycarbonyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-acetyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-acetoxy, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 4-dimethylamino, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 4-dimethylaminocarbonyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 4-methyloxycarbonyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 4-acetyl, R₂, R₃, and R are H. R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 4-acetoxy, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-CH₂F, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-cyano, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-ethoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 4-ethoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-chloromethoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 2-methyl, R₂ is 4-methylsulfonyl, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 4-bromo, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-cyclopropyl, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is trans-3-(2-methylcyclopropyl), R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ is 2-(2-fluoroethyl), and R₄ is H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ is 2-chloro, R₄ is 2-fluoro, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ and R₂ are both halogen, R₃ is 2-methyl, and R₄ is H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is 2-chloro, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is 2-(2-chloroethyl), R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 4-CF₃, R₃ is 2-hydroxymethyl, R₂ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ and R₂ are both H. R₃ is 3-methyl, R₄ is 2-chloro, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which one or both of R₁ and R₂ are CF₃, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is isothiazolyl, isoxazolyl, oxazolyl, oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl; R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, pyrimidinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl; oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolyl, isothiazolinyl, isothiazolidinyl, isothiazolidinonyl, indolyl, indolyl, oxindolyl, isoindolyl, quinolyl, isoquinolyl, or naphthyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 2-chloro, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 3-chloro, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 4-chloro, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 5-chloro, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 3-bromo, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 4-bromo, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 5-bromo, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 2-chloro, R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIA-1, in which R₁ is 3-chloro, R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which one or both of R₁ and R₂ are CF₃, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-CF₃, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-cyano, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-hydroxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 4-hydroxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-methoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-dimethylamino, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-dimethylaminocarbonyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-methyloxycarbonyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-acetyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-acetoxy, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 4-dimethylamino, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 4-dimethylaminocarbonyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 4-methyloxycarbonyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 4-acetyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 4-acetoxy, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-CH₂F, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-cyano, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-ethoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 4-ethoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-chloromethoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 2-methyl, R₂ is 4-methylsulfonyl, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 4-bromo, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-cyclopropyl, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is trans-3-(2-methylcyclopropyl), R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ is 2-(2-fluoroethyl), and R₄ is H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ is 2-chloro, R₄ is 2-fluoro, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In another more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ and R₂ are halogen, R₃ and R₄ are H, and R′ is methyl.

In another more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ and R₂ are halogen, R₃ and R₄ are H, and R′ is ethyl.

In another more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ and R₂ are halogen, R₃ and R₄ are H, and R′ is 1,2-chloropropan-3-yl.

In another more specific embodiment, this invention provides a compound of formula XIA-1, in which R₁ and R₂ are halogen, R₃ and R₄ are H, and R′ is 1-hydroxy-butan-3-yl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 4-(methylcarbamoyl), R₂ is 5-fluoro, R₃ and R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 4-acetamido, R₂ is 5-fluoro, R₃ and R₄ are H, and R′ is 1,2-dihydroxy-propan-3-yl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ and R₂ are 4-fluoro and 5-fluoro, R₃ and R₄ are H, and R′ is 2-hydroxyethyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ and R₂ are 4-chloro and 5-chloro, R₃ and R₄ are H, and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ and R₂ are 4-fluoro and 5-fluoro, R₃ and R₄ are H, and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 2-methoxymethyl, and R₂ is 3-chloro, R₃ and R₄ are H, and R′ is 1,2-dihydroxybutan-4-yl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 2-ethoxymethyl, and R₂ is 3-chloro, R₃ and R₄ are H, and R′ is 1,2-dihydroxybutan-3-yl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-methoxymethyl, R₂ is 4-chloro, R₃ and R₄ are H, and R′ is 1,2-dihydroxybutan-4-yl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-nitro, R₂ is 4-methoxy, R₃ and R₄ are H, and R′ is 1,2-dihydroxybutan-3-yl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 5-nitro, R₂-R₄ are H, and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-cyano, R₂-R₄ are H, and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 3-(2-methoxyethenyl), R₂-R₄ are H, and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ is 4-cyano, R₂-R₄ are H, and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-1, in which R₁ and R₂ are 3-chloromethyl and 4-chloromethyl, R₃ and R₄ are H, and R′ is 3-hydroxypropyl.

In another subgeneric embodiment, this invention provides a compound of formula XIA-2, where R₁-R′ are defined as for formula I.

In a more specific embodiment, this invention provides a compound of formula XIA-2 where R₁-R₄ are H and R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compound of formula XIA-2 where R₁-R₄ are H and R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compound of formula XIA-2 where R₁-R₄ are H and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In a more specific embodiment, this invention provides a compound of formula XIA-2 where R₁-R₄ are H and R′ is isopropyl, 2-butyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-duhydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound of formula XIA-2, where R₁ is amino, methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino, R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula XIA-2, where R₁ is nitro, cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl, R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In a more specific embodiment, this invention provides a compound of formula XIA-2, where R is 4-acetyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compound of formula XIA-2, where R₁ is 4-bromo, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2, where R₁ is 5-bromo, R₂ and R₃ are H, R₄ is 2-fluoro, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2, where R₁ is 5-cyano, R₂ is H, R₃ is 2-trifluoromethyl, R₄ is 2-fluoro, R′ is —(CH₂)_(n)—B, where n is 1, and B is 5-methyl-2-furyl, 5-methyl-2-pyrrolyl, or 3-pyrrolyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2, where R₁ is 4-fluoro, R₂ is 5-fluoro, R₃ is 3-acetamido, R₄ is 2-fluoro, R′ is —(CH₂)_(n)—B, where n is 1, and B is 5-methyl-2-furyl, 5-methyl-2-pyrrolyl, or 3-pyrrolyl.

In a more specific embodiment, this invention contemplates a compound of formula XIA-2 where R₁-R₄ are H and R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2 where R₁-R₄ are H and R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2 where R₁-R₄ are H and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-duhydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2, where R₁ and R₂ together, at positions 3 and 4, are fused cyclopentyl, R₃ and R₄ are H, and R′ is 1-hydroxy-butan-3-yl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2 in which R₁ and R₂ together, at positions 3 and 4, are fused cyclopentyl, R₃ and R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2 in which R₁ and R₂ together, at positions 4 and 5, are fused (2,3)-furyl, R₃ and R₄ are H, and R′ is 1,2-dihydroxy-propan-3-yl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2 in which R₁ and R₂ together, at positions 3 and 4, are fused (2,3)thienyl, R₃ and R₄ are H, and R′ is 2-hydroxyethyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2 in which R₁ and R₂ together, at positions 3 and 4, are fused cyclopentyl, R₃ and R₄ are H, and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention provides a compound of formula XIA-2, where R₁ is amino, methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino, R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula XIA-2, where R₁ is nitro, cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl, R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2, where R₁ and R₂ together, at positions 3 and 4, are fused cyclopentyl, R₃ and R₄ are H, and R′ is 1-hydroxy-butan-3-yl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2 in which R₁ and R₂ together, at positions 3 and 4, are fused cyclopentyl, R₃ and R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2 in which R₁ and R₂ together, at positions 4 and 5, are fused (2,3)-furyl, R₃ and R₄ are H, and R′ is 1,2-dihydroxy-propan-3-yl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2 in which R₁ and R₂ together, at positions 3 and 4, are fused (2,3)thienyl, R₃ and R₄ are H, and R′ is 2-hydroxyethyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2 in which R₁ and R₂ together, at positions 3 and 4, are fused cyclopentyl, R₃ and R₄ are H, and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2 in which R₁ and R₂ together are fused furyl, R₃ and R₄ are H, and R′ is 1,2-dihydroxybutan-4-yl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2 in which R₁ and R₂ together are fused cyclopentyl, R₃ and R₄ are H, and R′ is 1,2-dihydroxybutan-4-yl.

In another specific embodiment, this invention contemplates a compound of formula XIA-2 in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is 2-(2-chloroethyl), R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a more specific embodiment, this invention provides a compound of formula XIA-2 in which R₁ is 4-CF₃, R₃ is 2-hydroxymethyl, R₂ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention contemplates a compound of formula XIA-2 in which R₁ is 3-CH₂F, R₂ is 5-cyano, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another generic embodiment, this invention provides a compound of formula B, where R₁-R′ are defined as for formula A, where the dashed line represents an optional double bond, and where symbols L, T, U, V, and W— Z represent N, CH, or CR_(1, 2, or 4), provided that at least one of L, T, U, V, and W-Z is N, and further provided that no two nitrogen atoms are adjacent.

In one subgeneric embodiment, this invention provides a compound of formula XIB-1,

where all substituents are defined as for formula I.

In a more specific embodiment, this invention provides a compound of formula XIB-1, where R₁-R₄ are, independently, H, C₁-C₆ alkyl, hydroxy, or halogen, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, 1-pyrrolidonyl, 2,6-dimethyl-4-morpholyl, 4-morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compound of formula XIB-1, where R₁-R₄ are, independently, H, C₁-C₆ alkyl, hydroxy, or halogen, and R′ is C₁-C₄ alkyl, optionally substituted with one or two halogen atoms, hydroxy groups, or C₁-C₃ alkoxy groups.

In a still more specific embodiment, this invention provides a compound of formula XIB-1, where R₁-R₄ are, independently, H. C₁-C₄ alkyl, hydroxy, or halogen, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound of formula XIB-1 where one of R₁ and R₂ is H and the other is amino, methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino; R₃-R₄ are, independently, H, chloro, methyl, or hydroxy; and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula XIB-1, where one of R₁ and R₂ is H and the other is nitro, cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl; R₃-R₄ are, independently, H, chloro, methyl, or hydroxy; and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula XIB-1, where R₁ and R₂ are fused cyclohexyl or fused cyclopentyl, R₃ and R₄ are, independently, H, chloro, methyl, or hydroxy; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound of formula XIB-1, where R₁ and R₂ are fused benzo; R₃ and R₄ are, independently, H, chloro, methyl, or hydroxy; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound of formula XIB-1, wherein R₁ and R₂ are, independently, H or halogen, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In a more specific embodiment, this invention provides a compound of formula XIB-1, where R₁-R₃ are H, R₄ is 2-halo, 2-cyano, 2-hydroxy, or 2-methoxy, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is 4-methyl-1-piperazinyl, 1-piperidinyl, piperidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, 2-furyl, 2-tetrahydrofuryl, 1-pyrrolidonyl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compound of formula XIB-1, where R₁ is halo, R₂-R₄ are H and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, the invention contemplates a compound of formula XIB-1, where R₁ is chloro or bromo; R₂-R₄ are H; and R′ is isopropyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, or 2,3-dihydroxy-1-propyl.

In another embodiment, this invention provides a compound of formula XIB-2,

where substituents are defined as for formula I.

In a more specific embodiment, this invention provides a compound of formula XIB-2, where R₁-R₄ are, independently, H or halogen, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2-methoxyethyl, 1-hydroxy-2-propyl,1,2-dihydroxy-3-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound of formula XIB-2, where one of R₁ and R₂ is H and the other is amino, methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino, R₃-R₄ are H, and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula XIB-2, where one of R₁ and R₂ is H and the other is nitro, cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl, R₃-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula XIB-2, where R₁ and R₂ are H, R₃ is methyl, methoxy, acetamido, or acetyl, R₄ is nitro, cyano, halo, halomethyl, dimethylamino, or methylaminocarbonyl, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIB-2, where R₁ and R₂ are fused cyclohexyl or are both H, R₃ and R₄ are H, and R′ is isopropyl or 1-hydroxy-2-propyl.

Additional embodiments of generic structure B are shown below.

In more specific embodiments, the invention provides compounds according to any of formulas XIB-1 to XIB-43, wherein R₁-R₄ are all independently methyl, methoxy, ethyl, vinyl, ethynyl, halo, or H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, cyclopentyl, cyclopentenyl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In additional more specific embodiments, the invention provides compounds according to any of formulas XIB-1 to XIB-43, wherein R₁-R₄ are all independently halo, halomethyl, dihalomethyl, or H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is phenyl, pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In additional more specific embodiments, the invention contemplates compounds according to any of formulas XIB-1 to XIB-43, where R₁ is bromo; R₂-R₄ are all H; and R′ is isopropyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In additional more specific embodiments, the invention contemplates compounds according to any of formulas XIB-1 to XIB-43, where R₁ is chloro; R₂-R₄ are all H; and R′ is isopropyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In additional more specific embodiments, the invention contemplates compounds according to any of formulas XIB-1 to XIB-43, where R₃ is chloro; R₁, R₂, and R₄ are all H; and R′ is isopropyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In additional more specific embodiments, the invention contemplates compounds according to any of formulas XIB-1 to XIB-43, where R₄ is chloro or hydroxy; R₁-R₃ are all H; and R′ is isopropyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In still more specific embodiments, the invention contemplates compounds according to any of formulas XIB-1 to XIB-43, where R₁-R₄ are all H and R′ is isopropyl, 1-hydroxy-2-propyl, or 2,3-dihydroxy-1-propyl.

In still more specific embodiments, the invention contemplates compounds according to any of formulas XIB-1 to XIB-28 and XIB-30 to XIB-42, where R₁-R₃ are all H; R₄ is ortho to the amide group and is chloro or hydroxy; and R′ is isopropyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or (2-tetrahydrofuryl)methyl.

Additional contemplated examples of compounds according to formulas XIB-1 to XIB-43 are shown below.

Additional contemplated compounds for subgeneric embodiments XIA-1 and XIA-2 are shown in the tables below Cpd # Structure 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

In another generic embodiment, this invention provides a compound of formula XII below, where the dashed bond represents an optional double bond, and where symbols T-Z represent N, CH, or CR_(1, 2, or 4), that at most two of W, X, Y, and Z and at most 2 of T, U, and V are N;

where R₁-R₄ are, independently, hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₆ alkyl; O—C₁-C₆ alkyl; C₂-C₆ alkenyl; C₂-C₆ alkynyl; C₁-C₆ cycloalkyl; 2-methoxy ethenyl; CH₃OC(O); CH₃CH₂OC(O); C₁-C₅ alkyl-C(O)—; C₁-C₅ alkyl-C(O)O—; —NR₆R₇, —CH₂NR₆R₇, —NH—C(O)—R₆, —C(O)NR₈R₉; CH₃S(O)₂—, or —S(O)₂NR₈R₉, where R₆-R₉ are, independently, H or C₁-C₄ alkyl; or any of the pairs R₁ and R₂, R₆ and R₇, or R₈ and R₉ are attached to adjacent carbons and, together with the ring atoms to which they are attached, form an additional, fused, five- or six-membered ring, optionally containing one or two heteroatoms selected from O, N, and S, which ring may be aromatic or aliphatic; wherein all alkyl, alkenyl, and cycloalkyl groups and all rings are optionally substituted with 1-3 halogen atoms; R′ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; or R′ is —(CH₂)_(n)—B where n is 1 or 2 and B is a five- or six-membered ring or a 9- to 14-member fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds.

In one subgeneric embodiment, this invention provides a compound of formula XIIA-1,

where all substituents are defined as for formula XII.

In a more specific embodiment, this invention provides a compound of formula XIIA-1 where R₃ and R₄ are both H and R′ is —(CH₂)_(n)—B, where n is 1 or 2 and B is defined as above.

In another more specific embodiment, this invention provides a compound of formula XIIA-1 where R′ is C₁-C₆ alkyl or O—C₁-C₆ alkyl, both optionally substituted as described above.

In another more specific embodiment, this invention provides a compound of formula XIIA-1 where R₃ and R₄ are both H and R′ is C₁-C₆ alkyl or O—C₁-C₆ alkyl, both optionally substituted as described above.

In another more specific embodiment, this invention provides a compound of formula XIIA-1, where R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula XIIA-1, where R₁ is amino, methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino, R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula XIIA-1, where R₁ is nitro, cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl, R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are both halogen, R₃ is 2-methyl, and R₄ is H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is 2-chloro, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is 2-(2-chloroethyl), R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 4-CF₃, R₃ is 2-hydroxymethyl, R₂ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is 2-chloro, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which one or both of R₁ and R₂ are CF₃, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is isothiazolyl, isoxazolyl, oxazolyl, oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl; R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, pyrimidyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl; oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolyl, isothiazolinyl, isothiazolidinyl, isothiazolidinonyl, indolyl, indolyl, oxindolyl, isoindolyl, quinolyl, isoquinolyl, and naphthyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 2-chloro, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 3-chloro, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 4-chloro, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 5-chloro, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 3-bromo, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 4-bromo, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 5-bromo, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 2-chloro, R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 3-chloro, R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which one or both of R₁ and R₂ are CF₃, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 3-CF₃, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-cyano, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-hydroxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 4-hydroxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-methoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 3-dimethylamino, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 3-dimethylaminocarbonyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 3-methyloxycarbonyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 3-acetyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 3-acetoxy, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 4-dimethylamino, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 4-dimethylaminocarbonyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 4-methyloxycarbonyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 4-acetyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 4-acetoxy, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 3-CH₂F, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-cyano, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-ethoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 4-ethoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-chloromethoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 2-methyl, R₂ is 4-methylsulfonyl, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 4-bromo, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is trans-3-(2-methylcyclopropyl), R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ is 2-(2-fluoroethyl), and R₄ is H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ is 2-chloro, R₄ is 2-fluoro, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are both halogen, R₃ is 2-methyl, and R₄ is H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is 2-chloro, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is 2-(2-chloroethyl), R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 4-CF₃, R₃ is 2-hydroxymethyl, R₂ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is 2-chloro, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which one or both of R₁ and R₂ are CF₃, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is isothiazolyl, isoxazolyl, oxazolyl, oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl; R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, pyrimidyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl; oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolyl, isothiazolinyl, isothiazolidinyl, isothiazolidinonyl, indolyl, indolyl, oxindolyl, isoindolyl, quinolyl, isoquinolyl, and naphthyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 2-chloro, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 3-chloro, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 4-chloro, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 5-chloro, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 3-bromo, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 4-bromo, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 5-bromo, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 2-chloro, R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates the compound of formula XIIA-1 in which R₁ is 3-chloro, R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which one or both of R₁ and R₂ are CF₃, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 3-CF₃, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-cyano, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-hydroxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 4-hydroxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-methoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 3-dimethylamino, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 3-dimethylaminocarbonyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 3-methyloxycarbonyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 3-acetyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 3-acetoxy, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 4-dimethylamino, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 4-dimethylaminocarbonyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 4-methyloxycarbonyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 4-acetyl, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 4-acetoxy, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates a compound of formula XIIA-1 in which R₁ is 3-CH₂F, R₂, R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-cyano, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-ethoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 4-ethoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-chloromethoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 2-methyl, R₂ is 4-methylsulfonyl, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 4-bromo, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂-R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is trans-3-(2-methylcyclopropyl), R₂ is 4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ is 2-(2-fluoroethyl), and R₄ is H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ is 2-chloro, R₄ is 2-fluoro, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In another more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are H, and R′ is methyl, ethyl, isopropyl, or sec-butyl.

In another more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is halogen, R₂-R₄ are H, and R′ is methyl, ethyl, isopropyl, or sec-butyl.

In another more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are H, and R′ is 1,2-chloropropan-3-yl.

In another more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are H, and R′ is l-hydroxy-butan-3-yl.

In another more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ is bromo, R₂-R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are H, and R′ is 1,2-dihydroxy-propan-3-yl.

In another more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are H, and R′ is 2-hydroxyethyl.

In another more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are H, and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R are H, and R′ is 1,2-dihydroxybutan-4-yl.

In another more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are C₁-C₆ alkyl, and R′ is 1,2-dihydroxybutan-3-yl.

In another more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are H, and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention provides a compound of formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are H, and R′ is 3-hydroxypropyl.

In another more specific embodiment, this invention provides a compound of formula XIIA-1, where R₁ and R₂ are fused cyclohexyl or fused cyclopentyl, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound of formula XIIA-1, where R₁ and R₂ are benzo, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula XIIA-1, where R₁ and R₂, at positions 2 and 3, are fused cyclopentyl, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula XIIA-1, where R₁ and R₂, at positions 3 and 4, are benzo, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates a compound of formula XIIA-1, where R₁ and R₂, at positions 3 and 4, are benzo, said benzo bearing fluoro at each ortho position, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

Additional contemplated compounds for generic embodiment XIIA-1 are shown in the table below Cpd # Structure 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

In an additional subgeneric embodiment, this invention provides a compound of formula XIIB-1,

where R₁-R′ are defined as for formula A.

In a more specific embodiment, this invention provides a compound of formula XIIB-1, where R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound of formula XIIB-1, where R₁-R₄ are, independently, H, C₁-C₃ alkyl, or halogen, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In another subgeneric embodiment, this invention provides a compound of formula XIIB-2 below,

In a more specific embodiment, this invention provides a compound of formula XIIB-2 where R₁-R₄ are H and R′ is isopropyl, 2-butyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compound of formula XIIB-2, where R₁ is amino, methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino, R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula XIIB-2, where R₂ is amino, methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino, R₁ and R₂-R₄ are H, and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compound of formula XIIB-2, where R₁ is nitro, cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl, R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

Examples of additional embodiments of the aza-substituted type are shown below, along with prophetic examples of each. In the first column, non-carbon ring members of T-Z of formula XII are identified. Generic Structure: Formula XII, where Example X = N XIIB-3

XIIB-3a X and Z = N XIIB-4

XIIB-4a X and T = N XIIB-5

XIIB-5a T = N XIIB-6

XIIB-6a U = N XIIB-7

XIIB-7a X and U = N XIIB-8

XIIB-8a U, X, and Z = N XIIB-9

XIIB-9a U and W = N XIIB-10

XIIB-10a U and Z are N XIIB-11

XIIB-11a X, V, and T = N XIIB-12

XIIB-12a

In additional more specific embodiments, the invention provides compounds according to any of formulas XIIB-1 to XIIB-12, wherein R₁-R₄ are all independently halo, halomethyl, methyl, methoxy, ethyl, vinyl, ethynyl, or H, and R₅ is —(CH₂)_(n)—B, where n is 1 or 2, and B is imidazolyl, cyclopentyl, cyclopenten-3-yl, cyclohexyl, cyclohexen-2-yl, phenyl, pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In additional more specific embodiments, the invention contemplates compounds according to any of formulas XIIB-1 to XIIB-12, where R₁ is bromo, R₂-R₄ are all H and R₅ is isopropyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In still more specific embodiments, the invention contemplates compounds according to any of formulas XIIB-1 to XIIB-12, where R₁-R₄ are all H and R₅ is isopropyl or 2,3-dihydroxy-1-propyl.

This invention also contemplates other patterns of aza-substitution and poly-aza-substitution not depicted in the examples shown above.

Experimental Details

Synthesis

Compounds of this invention are prepared according to the schemes below.

I. Synthesis of Contemplated Compounds

The choice of synthetic strategy is not critical to the practice of this invention. Suitable approaches include both those in which commercially available or previously synthesized isothiazoles are modified and those involving cyclization of a thiocarbamoyl acetamide to form the isothiazole ring system.

Scheme 1 illustrates a reaction of 2-cyanoacetamide with an isothiocyanate to an intermediate, and subsequent ring closure by oxidation followed by amination by heating the cyano compound with an amine (e.g., isopropylamine, 2-amino-propan-1-ol) to provide the amidine 4. This general strategy can be used for compounds of formulas II-VI.

More specifically, in step 1 of Scheme 1,2-cyanoacetamide was treated with a strong base (e.g., KOH) and then with a substituted phenyl isothiocyanate 1 in N,N-dimethylformamide (DMF) at a temperature ranging from about −10° C. to 60° C., preferably about 25° C., for a period of about 8 to 24 hours, preferably about 16 hours, to produce compound 2. Then, in step 2 of Scheme 1, compound 2 (in the same reaction vessel as step 1) was treated at about 0° C. with aqueous chloramine solution for about 12 hours, and compound 3 was isolated.

Alternatively, the reaction mixture of step 1 was concentrated and diluted with water, followed by acidification with aqueous hydrochloric acid solution. Filtration and washing with water afforded compound 2. In an organic solvent, preferably ethyl acetate, compound 2 was treated with bromine to provide isothiazole 3. In step 3 of Scheme 1, compound 3 was agitated with an alkylamine (including a hydroxyalkylamine) in ethanol, in a sealed reaction vessel at about 80-120° C., preferably about 100° C., for about 16 to 24 hours, preferably 18 hours, to provide amidine 4 in good yield after chromatography.

Scheme 1 includes the synthesis of compounds wherein R₁ is a phenoxy or phenylthio group. In a variation of Scheme 1, a pyridyl, naphthyl, or quinolyl isothiocyanate may be used in place of the phenyl isothiocyanate that is illustrated. Compounds in which R₁ is a benzyl, benzoyl, phenylazido, or phenylacetyl group are prepared using commercially available precursors such as p-nitro benzophenone, p-nitro diphenylmethane, and p-nitro diphenylazide. In a variation of Scheme 1, a pyridyl, naphthyl, or quinolyl isothiocyanate may be used in place of the phenyl isothiocyanate that is illustrated.

Preparation of Isothiazoles Using 4-Substituted Anilines

The p-phenoxy phenylisothiocyanates can be synthesized by condensing the appropriately substituted p-fluoronitrobenzene with a phenol or aniline, as shown below.

General Procedure for 4-Substituted Phenols and Anilines

Preparation of Isothiocyanates from Anilines

A mixture comprising a 4-fluoronitrobenzene 6 (0.02 mol), a suitable aniline or phenol 7 (0.022 mol), and potassium carbonate (0.022 mol) in 40 ml of anhydrous DMF was heated overnight at 150° C. with stirring. After cooling to room temperature, the reaction mixture was poured into 500 ml of ice water and stirred for 30 min. The precipitate was collected by filtration, washed with water, and dried in vacuo to give a 4-substituted nitrobenzene 8. The nitrobenzene 8 was dissolved in 100-200 ml of ethanol and stirred for 5-6 hours under hydrogen in the presence of catalyst 10% Pd—C (50-100 mg), at atmospheric pressure and ambient temperature. The catalyst was removed by filtration, and the filtrate was concentrated to dryness to give the crude substituted aniline 9, which was used for the next step without further purification.

Method 1: The appropriate aniline 10 (30 mmol) was added to a biphasic mixture of CHCl₃ and saturated aqueous NaHCO₃ (1:1, v/v, 247 ml), followed by dropwise addition at room temperature, with stirring, of a solution of thiophosgene (30 mmol) in dichloromethane (20 ml). The mixture was stirred vigorously at room temperature for 1 hour. The bottom layer of the mixture was separated, and the aqueous layer was extracted twice with CHCl₃. The combined organic solution was washed with water, dried over MgSO₄, and evaporated to give isocyanate 11 as a yellow solid, which was used for the next step without further purification.

Method 2: To a solution of aniline (30 mmol) and DBU (60 mmol) in 60 ml of anhydrous dichloromethane, a solution of thiophosgene (30 mmol) in 20 ml of dry dichloromethane was added dropwise with stirring at room temperature over 30 minutes. The reaction mixture was diluted with 200 ml of chloroform and washed with 1N HCl solution (300 ml×2) and water (300 ml) respectively. The chloroform solution was dried over anhydrous sodium sulfate, and the solvent was evaporated in vacuo. The residue was purified by silica gel column to give pure isothiocyanates.

(3) Preparation of Isothiazoles (see Scheme 1)

3-Hydroxy-5-phenylamino-isothiazol-4-carbonitrile

Method 1: To a cooled suspension of finely ground potassium hydroxide (0.337 g, 6 mmol) in DMF (8 ml) was added cyanoacetamide (0.505 g, 6 mmol) followed by addition of 4-methoxyphenyl isothiocyanate (0.83 ml, 6 mmol). The reaction mixture was stirred at room temperature for 24 hours and treated with aqueous chloramine (30 ml) at 0° C. The mixture was further stirred at room temperature for 12 hours, and evaporated to give a residue, which was partitioned between water and ethyl acetate. The aqueous layer was washed twice with ethyl acetate, then cooled to 0° C. and acidified with 1N HCl solution to about pH-3. The precipitate was filtered and washed with water and dried in vacuo to afford a yellow powder (0.95 g, 73%).

Method 2: Condensation of isothiocyanate with 2-cyanoacetamide: Procedure 1: To a cooled suspension of finely ground potassium hydroxide (0.337 g, 6 mmol) in DMF (8 ml) was added cyanoacetamide (0.505 g, 6 mmol), followed by addition of 4-methoxyphenyl isothiocyanate (0.83 ml, 6 mmol). The reaction mixture was stirred at room temperature for 16 hours and concentrated to give a syrup, which was diluted with water and acidified with 1 N aqueous HCl solution. The suspension was filtered, and the solid was washed with water and dried in vacuo. Procedure 2: To a solution of potassium tert-butoxide (20 mmol) in 20 ml of anhydrous THF was added 2-cyanoacetamide (20 mmol). The mixture was cooled to 5° C. and a solution of isothiocyanates (20 mmol) in 5 ml of dry THF was added dropwise with stirring under argon. After 15 min with stirring at 5° C., the reaction mixture was warmed to room temperature and stirred for another 1 h. The reaction mixture was poured into 1000 ml of ice water and neutralized with 2% HCl solution to pH<7. The solid was filtered and washed with water. After drying in vacuo, the crude product was obtained and it is pure enough for next step (Yield: 72-97%).

Cyclization: The above dried solid was dissolved in ethyl acetate (30 ml), and a solution of bromine (0.31 ml, 6 mmol) in ethyl acetate (25 ml) was added drop wise into the mixture. After 1 hour of stirring at room temperature, the reaction mixture was filtered, and the solid was washed with ethyl acetate and dried in vacuo to afford a yellow powder (0.86 g, 66%).

Preparation of 5-benzimidazole, oxazole, thiazole, and isothiazole carboxamidines

The 2-(4-aminophenyl)benzoxazole, benzothiazole, or benzimidazole was prepared by condensation of the appropriate aniline derivative with p-amino benzoic acid using polyphosphoric acid. The product was converted to the corresponding isothiocyanate with thiophosgene and subsequently condensed with cyanoacetamide to form the thiocarbamoyl cyanoacetamide. Treatment with bromine afforded the cyano hydroxy thiazole, which was converted to carboxamidine by treatment with the appropriate amide, as shown above.

PREPARATION OF EXAMPLES

A typical procedure for synthesis of isothiazole carboxamidines is that employed for synthesis of 3-hydroxy-N-isopropyl-5-(4-phenoxyphenylamino)-isothiazole-4-carboxamidine:

A mixture of 3-hydroxy-4-cyano-5-(4-phenoxyphenylamino)isothiazole (5 g) and isopropylamine (25 ml) in 250 ml of ethanol was placed into a high-pressure reaction equipment and heated to 120° C. with stirring for 9 hours. The reaction mixture was cooled to room temperature, and the solvent was removed under vacuum. The residue was treated with 500 ml of diethyl ether, and the precipitates were filtered and washed with diethyl ether. The filtrates were evaporated to dryness, and the residue was purified by silica gel column chromatography (chloroform/methanol, 60:1) to give 3.51 g (59%) of product as a foam, which was recrystallized from methanol to give yellowish crystals. MS: 368; ¹H NMR(DMSO-d6): 10.44 (brs, ½H, NH, D₂O exchangeable), 9.81 (brs, ½H, NH, D₂O exchangeable), 9.51 (brs, ½H, NH, D₂O exchangeable), 9.15 (brs, ½H, NH, D₂O exchangeable), 8.36 (s, 1H, OH, D₂O exchangeable), 7.87 (brs, ½H, NH, D₂O exchangeable), 7.66 (brs, ½H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H, J=7.5 Hz, ArH), 6.96 (m, 6H, ArH), 3.85 (m, 1H, CH), 1.20 (d, 6H, J=6.3 Hz, 2×CH₃).

The isothiazole carboxamidines listed in table 2 were synthesized by the procedure above. Most reactions were run using 100-200 mg of starting materials in about 20-30 ml of ethanol at 90° C. for 24-48 hours. In most cases products were purified by silica gel column chromatography. Some compounds were purified by preparative HPLC or TLC.

N-Cyclohexylmethyl-3-hydroxy-5-(3-phenoxy-phenylamino)-isothiazole-4-carboxamidine

To a suspension of 85% powdered KOH in 20 ml DMF was added 1.74 g of cyanoacetamide at room temperature. The solution was stirred at room temperature for 15 minutes and then cooled in a water bath at room temperature. To this solution 4.7 g of 3-phenoxy-phenyl isothiocyanate was added dropwise. The solution exothermed slightly with the internal temperature rising to 28° C. during the addition. The solution was stirred at room temperature for 16 h, then diluted with 150 ml water and extracted with ethyl acetate to remove small amounts of starting material and by-products. The aqueous layer was isolated and acidified with 1N HCl to pH 1 with vigorous stirring. The resulting tan precipitate was filtered, washed with water, and dried for 16 hours in a vacuum oven to afford 4.66 g of 2-cyano-2-(3-phenoxy-phenylthiocarbamoyl)-acetamide.

The product of the previous step was suspended in 100 ml ethyl acetate and stirred vigorously. A solution of 767 μl Br₂ in 25 ml ethyl acetate was added via addition funnel over 30 minutes. After 1.5 h, saturated aqueous NaHCO₃ was added, and the resulting biphasic mixture was stirred for 30 minutes. The mixture was filtered and washed with ethyl acetate, followed by water and dried in vacuo to afford 2.75 g (43%) of 3-hydroxy-5-(3-phenoxy-phenylamino)-isothiazole-4-carbonitrile as a tan solid. To a suspension of 190 mg of this material in 10 ml ethyl alcohol in a 40 ml Teflon-lined screw-thread vial was added 500 μl cyclohexyl methylamine and heated to 80° C. After 18 h, the reaction was cooled and the solvent evaporated. The residue was purified by preparative HPLC to afford 26 mg (10%) of N-cyclohexylmethyl-3-hydroxy-5-(3-phenoxy-phenylamino)-isothiazole-4-carboxamidine as a tan solid. ¹H NMR((CD₃)₂SO) δ 0.969 m 2H, 1.161 m 3H, 1.718-1.510 m 6H, 3.109 t 2H J=6.3 Hz, 6.473 s 1H, 6.633 dd 1H J=2.1 and 7.8 Hz, 6.698 dd 1H J=1.2 and 7.8 Hz, 7.014 d 2H J=7.8 Hz, 7.130 t 1H J=7.5 Hz, 7.276 t 1H, J=7.2 Hz, 7.381 t 2H J=8.1 Hz, 7.691 bs ½H, 8.416 s 1H, 9.099 bs ½H, 9.745 bs ½H, 10.566 bs ½H. MS m/z. 423(M+1), 421(M−1).

Preparation of 5-[4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylamino]-3-hydroxy-N-isopropyl-isothiazole-4-carboxamidine and 5-[4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylamino]-3-hydroxy-N-(2-hydroxy-1-methyl-ethyl)-isothiazole-4-carboxamidine

1-(2,5-Dichloro-phenoxy)-2-fluoro-4-nitro-benzene

A mixture of 3,4-difluoronitrobenzene (3.2 g, 0.02 mol), 2,5-dichlorophenol (3.59 g, 0.022 mol), and potassium carbonate (3.0 g, 0.022 mol) in 25 ml of anhydrous DMF was heated to 150° C. with stirring overnight. After cooling to room temperature, the reaction mixture was poured into 500 ml of ice water and stirred for 30 min. The precipitates were collected by filtration, washed with water, and dried in vacuo to give 5.72 g (94.7%) of crude product.

4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylamine

A mixture of 1-(2,5-dichloro-phenoxy)-2-fluoro-4-nitro-benzene (0.5 g, 1.7 mmol) and tin chloride (1.57 g, 8.3 mmol) in 30 ml of anhydrous ethanol was heated to 70° C. under argon and stirred for 4 hours. The solution was allowed to cool and then poured into ice. The solution was made slightly basic (pH 7-8) by addition of saturated aqueous sodium bicarbonate solution, then extracted with ethyl acetate. The organic phase was thoroughly washed with brine and dried treated with anhydrous sodium sulfate. Evaporation of the solvent left a yellow oily product which was used for the next step without further purification.

4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylisothiocyanate

4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylamine (1.36 g, 5 mmol) was dissolved in 150 ml of chloroform and 100 ml of saturated aqueous sodium bicarbonate was added. To this biphasic mixture was added dropwise a solution of thiophosgene (0.39 ml, 5 mmol) in 30 ml of chloroform at room temperature with vigorous stirring. The mixture was stirred vigorously for 1 hour at room temperature. The bottom layer of the mixture was separated, and the aqueous layer was extracted twice with CHCl₃. The combined organic solution was washed with water, dried over Mg₂SO₄ and evaporated to give 1.53 g (97.4%) of crude product used for next step without further purification.

2-Cyano-2-[4-(2,5-dichloro-phenoxy)-3-fluoro-phenylthiocarbamoyl]-acetamide

To a solution of potassium tert-butoxide (0.6 g, 5.36 mmol) in 10 ml of anhydrous THF was added 2-cyanoacetamide (0.45 g, 5.36 mmol) under argon. The mixture was cooled to 5° C. and added dropwise to a solution of 4-(2,5-dichloro-phenoxy)-3-fluoro-phenylisothiocyanate (1.53 g, 4.87 mmol) in 5 ml of dry THF with stirring under argon. After 15 min of stirring at 5° C., this reaction mixture was warmed to room temperature and stirred for another 2 h. The reaction mixture was poured into 200 ml of ice water with stirring and acidified with 10% HCl. The solid was filtered and washed with water. After drying in vacuo, the crude product (1.6 g, 82.5%) was obtained in sufficient purity for the next step.

5-[4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylamino]-3-hydroxy-isothiazole-4-carbonitrile

2-Cyano-2-[4-(2,5-dichloro-phenoxy)-3-fluoro-phenylthiocarbamoyl]-acetamide (1.6 g, 4 mmol) was dissolved in anhydrous ethyl acetate (60 ml) and a solution of bromine (0.2 ml, 4 mmol) in anhydrous ethyl acetate (10 ml) was added dropwise into the mixture with stirring at room temperature. After addition, the reaction mixture was stirred for another 3 hours. The precipitate was filtered and the solid was washed with ethyl ether and suspended in a saturated sodium bicarbonate with stirring for 10 min. The solid was filtered, then washed with water and dried in vacuo to afford a white powder.

Exemplary Physical Data

5-[4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylamino]-3-hydroxy-N-isopropyl-isothiazole-4-carboxamidine

A mixture of 5-[4-(2,5-dichloro-phenoxy)-3-fluoro-phenylamino]-3-hydroxy-isothiazole-4-carbonitrile (0.2 g) and isopropylamine (5 ml) in 20 ml of ethanol was placed into a high-pressure reaction apparatus and heated to 100° C. overnight. The reaction mixture was cooled to room temperature, and the solvent was removed in vacuo. The residue was chromatographed by silica gel column (chloroform/methanol, 40:1) to give the desired product as a light yellow solid. MS: 454; ¹H NMR (DMSO-d₆, 300 MHz): δ 10.28 (brs, ½H, NH, D₂O exchangeable), 9.62 (brs, 1H, NH, D₂O exchangeable), 9.31 (brs, ½H, NH, D₂O exchangeable), 8.57 (s, 1H, OH, D₂O exchangeable), 7.88 (brs, 1H, NH, D₂O exchangeable), 7.61 (d, 1H, J=8.7 Hz, ArH), 7.22 (dd, 1H, J=2.1, 8.7 Hz, ArH), 7.16 (t, 1H, J=8.7 Hz, ArH), 6.99 (dd, 1H, J=2.1, 12.6 Hz, ArH), 6.88 (d, 1H, J=2.1 Hz, ArH), 6.83 (dd, 1H, J=2.1, 8.7 Hz, ArH), 3.85 (m, 1H, CH), 1.20 (d, 6H, J=6.3 Hz, 2×CH₃).

5-[4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylamino]-3-hydroxy-N-(2-hydroxy-1-methyl-ethyl)-isothiazole-4-carboxamidine

A mixture of 5-[4-(2,5-dichloro-phenoxy)-3-fluoro-phenylamino]-3-hydroxy-isothiazole-4-carbonitrile (0.2 g) and DL-2-amino-1-propanol (0.7 g) in 20 ml of ethanol was placed in a high-pressure reaction equipment and heated to 100° C. overnight. The reaction mixture was cooled to room temperature and the solvent was removed in vacuo. The residue was chromatographed by silica gel column (chloroform/methanol, 25:1) to give the desired product as a light yellow solid. MS: 470; ¹H NMR (DMSO-d₆, 300 MHz): δ 10.60 (brs, ½H, NH, D₂O exchangeable), 9.69 (brs, ½H, NH, D₂O exchangeable), 9.22 (brs, ½H, NH, D₂O exchangeable), 8.55 (s, 1H, OH, D₂O exchangeable), 7.91 (brs, ½H, NH, D₂O exchangeable), 7.70 (brs, ½H, NH, D₂O exchangeable), 7.61 (d, 1H, J=8.7 Hz, ArH), 7.22 (dd, 1H, J=2.1, 8.7 Hz, ArH), 7.16 (t, 1H, J=8.7 Hz, ArH), 6.99 (dd, 1H, J=2.1, 12.6 Hz, ArH), 6.88 (d, 1H, J=2.1 Hz, ArH), 6.83 (dd, 1H, J=2.1, 8.7 Hz, ArH), 5.09 (brs, 1H, OH), 3.80 (m, 1H, CH), 3.49 (m, 1H, CH). 3.44 (m, 1H, CH), 1.15 (d, 3H, J=6.3 Hz, CH₃).

3-Hydroxy-N-(3-hydroxy-2,2-dimethyl-propyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

¹H NMR (DMSO-d₆, 300 MHz) δ 10.64 (broad s, ½H), 9.81 (broad s, ½H), 9.15 (broad s, 1H), 8.38 (broad s, 1H), 7.64 (broad s, ½H), 7.40 (apparent d, J=7.2 Hz, 2H), 7.14 (apparent t, J=7.2 Hz, 1H), 7.01 (s, 6H), 4.90 (broad s, 1H), 3.24 (s, 2H), 3.18 (s, 2H), 0.941 (s, 6H). MS (EI) m/z 413 (M+1)⁺.

3-Hydroxy-N-(4-hydroxy-butyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

¹H NMR (DMSO-d₆, 300 MHz) δ 11.21 (broad s, ½H), 10.59 (broad s, ½H), 10.38 (broad s, ½H), 9.92 (broad s, ½H), 9.15 (s, 1H), 8.66 (broad s, ½H), 8.48 (broad s, ½H), 8.17 (t, J=8.4 Hz, 2H), 7.89 (t, J=7.2 Hz, 1H), 7.77 (d, J=5.4 Hz, 1H), 7.76 (s, 5H), 5.30 (t, J=4.8 Hz, 1H), 4.23 (q, J=6.0 Hz, 2H), 4.20-4.08 (m, 2H), 2.41-2.28 (m, 4H).

3-Hydroxy-N-(2-hydroxy-ethyl)-5-[4-(pyrimidin-5-yloxy)-phenylamino]-isothiazole-4-carboxamidine

¹H NMR (DMSO-d₆, 300 MHz) δ 11.62 (broad s, ½H), 9.86 (broad s, ½H), 9.72 (broad s, ½H), 9.22 (broad s, ½H), 9.01 (s, 1H), 8.62 (s, 2H), 8.44 (s, 1H), 7.91 (broad s, ½H), 7.68 (broad s, ½H), 7.15 (d, J=8.7 Hz, 2H), 7.05 (t, J=9.0 Hz, 2H), 5.05 (t, J=5.1 Hz, 1H), 3.64 (apparent d, J=5.1 Hz, 2H), 3.38 (apparent t, J=5.7 Hz, 2H).

N-tert-Butyl-3-hydroxy-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

¹H NMR (DMSO-d₆, 300 MHz) δ 10.93 (broad s, ½H), 10.15 (broad s, ½H), 9.94 (broad s, ½H), 9.48 (broad s, ½H), 8.47 (broad s, 1H), 7.41 (t, J=8.1 Hz, 2H), 7.14 (t, J=7.2 Hz, 1H), 7.02 (d, J=5.4 Hz, 2H), 7.01 (s, 5H), 1.45 (s, 9H). MS (EI) m/z 381 (M−1)⁺.

3-Hydroxy-N-(4-hydroxy-cyclohexyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

¹H NMR (DMSO-d₆, 300 MHz) δ 10.56 (broad s, ½H), 9.83 (broad s, ½H), 9.61 (broad s, ½H), 9.18 (broad s, ½H), 8.41 (broad s, 1H), 7.98 (broad s, ½H), 7.73 (broad s, ½H), 7.41 (t, J=7.8 Hz, 2H), 7.14 (t, J=7.5 Hz, 1H), 7.01 (d, J=5.4 Hz, 1H), 7.00 (s, 5H), 4.66 (d, J=4.5 Hz, 1H), 3.59-3.53 (m, 2H), 2.00 (broad s, 2H), 1.85 (broad s, 2H), 1.34 (broad s, 4H). MS (EI) m/z 423 (M−1)⁺.

3-Hydroxy-N-(2-hydroxy-1-methyl-ethyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 384; ¹H NMR(DMSO-d6): 10.60 (brs, ½H, NH, D₂O exchangeable), 9.83 (brs, ½H, NH, D₂O exchangeable), 9.61 (brs, ½H, NH, D₂O exchangeable), 9.15 (brs, ½H, NH, D₂O exchangeable), 8.33 (s, 1H, OH, D₂O exchangeable), 7.85 (brs, ½H, NH, D₂O exchangeable), 7.58 (brs, ½H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H, J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 5.06 (t, 1H, J=5.1 Hz, OH, D₂O exchangeable), 3.78 (m, 1H, CH), 3.47 (m, 1H, CH), 3.43 (m, 1H, CH), 1.15 (d, 3H, J=6.3 Hz, CH₃).

3-Hydroxy-N-[(S)-2-hydroxy-1-methyl-ethyl]-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 384; ¹H NMR(DMSO-d6): 10.60 (brs, ½H, NH, D₂O exchangeable), 9.84 (brs, ½H, NH, D₂O exchangeable), 9.60 (brs, ½H, NH, D₂O exchangeable), 9.17 (brs, ½H, NH, D₂O exchangeable), 8.33 (s, 1H, OH, D₂O exchangeable), 7.85 (brs, ½H, NH, D₂O exchangeable), 7.58 (brs, ½H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H, J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 5.06 (t, 1H, J=5.1 Hz, OH, D₂O exchangeable), 3.78 (m, 1H, CH), 3.47 (m, 1H, CH), 3.42 (m, 1H, CH), 1.15 (d, 3H, J=6.3 Hz, CH₃).

3-Hydroxy-N-[(R)-2-hydroxy-1-methyl-ethyl]-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 384; ¹H NMR(DMSO-d6): 10.60 (brs, ½H, NH, D₂O exchangeable), 9.84 (brs, ½H, NH, D₂O exchangeable), 9.59 (brs, ½H, NH, D₂O exchangeable), 9.17 (brs, ½H, NH, D₂O exchangeable), 8.34 (s, 1H, OH, D₂O exchangeable), 7.85 (brs, ½H, NH, D₂O exchangeable), 7.59 (brs, ½H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H, J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 5.06 (t, 1H, J=5.1 Hz, OH, D₂O exchangeable), 3.78 (m, 1H, CH), 3.48 (m, 1H, CH), 3.42 (m, 1H, CH), 1.15 (d, 3H, J=6.3 Hz, CH₃).

3-Hydroxy-N-(1-hydroxymethyl-propyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 398; ¹H NMR(DMSO-d6): 10.61 (brs, ½H, NH, D₂O exchangeable), 9.83 (brs, ½H, NH, D₂O exchangeable), 9.62 (brs, ½H, NH, D₂O exchangeable), 9.15 (brs, ½H, NH, D₂O exchangeable), 8.34 (s, 1H, OH, D₂O exchangeable), 7.83 (brs, ½H, NH, D₂O exchangeable), 7.56 (brs, ½H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H, J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 5.00 (t, 1H, J=5.1 Hz, OH, D₂O exchangeable), 3.62 (m, 1H, CHN), 3.47 (m, 2H, CH₂O), 1.62 (m, 1H, CHMe), 1.50 (m, 1H, CHMe), 0.90 (t, 3H, J=7.2 Hz, CH₃).

3-Hydroxy-N-[(S)-1-hydroxymethyl-propyl]-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 398; ¹H NMR(DMSO-d6): 10.59 (brs, ½H, NH, D₂O exchangeable), 9.82 (brs, ½H, NH, D₂O exchangeable), 9.61 (brs, ½H, NH, D₂O exchangeable), 9.16 (brs, ½H, NH, D₂O exchangeable), 8.33 (s, 1H, OH, D₂O exchangeable), 7.83 (brs, ½H, NH, D₂O exchangeable), 7.56 (brs, ½H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H, J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 5.00 (t, 1H, J=5.1 Hz, OH, D₂O exchangeable), 3.62 (m, 1H, CHN), 3.47 (m, 2H, CH₂O), 1.62 (m, 1H, CHMe), 1.49 (m, 1H, CHMe), 0.90 (t, 3H, J=7.2 Hz, CH₃).

3-Hydroxy-N-[(R)-1-hydroxymethyl-propyl]-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 398; ¹H NMR(DMSO-d6): 10.59 (brs, ½H, NH, D₂O exchangeable), 9.83 (brs, ½H, NH, D₂O exchangeable), 9.60 (brs, ½H, NH, D₂O exchangeable), 9.15 (brs, ½H, NH, D₂O exchangeable), 8.33 (s, 1H, OH, D₂O exchangeable), 7.83 (brs, ½H, NH, D₂O exchangeable), 7.58 (brs, ½H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H, J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 5.00 (t, 1H, J=5.1 Hz, OH, D₂O exchangeable), 3.62 (m, 1H, CHN), 3.47 (m, 2H, CH₂O), 1.62 (m, 1H, CHMe), 1.49 (m, 1H, CHMe), 0.90 (t, 3H, J=7.2 Hz, CH₃).

3-Hydroxy-N-(1-hydroxymethyl-2-methyl-propyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 412; ¹H NMR(DMSO-d6): 10.62 (brs, ½H, NH, D₂O exchangeable), 9.81 (brs, ½H, NH, D₂O exchangeable), 9.68 (brs, ½H, NH, D₂O exchangeable), 9.15 (brs, ½H, NH, D₂O exchangeable), 8.36 (s, 1H, OH, D₂O exchangeable), 7.82 (brs, ½H, NH, D₂O exchangeable), 7.56 (brs, ½H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H, J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 4.97 (t, 1H, J=5.1 Hz, OH, D₂O exchangeable), 3.58 (m, 1H, CHN), 3.49 (m, 2H, CH₂O), 1.96 (m, 1H, CHMe), 1.49 (m, 1H, CHMe), 0.92 (d, 6H, J=6.9 Hz, 2×CH₃).

3-Hydroxy-N-(2-hydroxy-propyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 384; ¹H NMR(DMSO-d6): 10.62 (brs, ½H, NH, D₂O exchangeable), 9.82 (brs, ½H, NH, D₂O exchangeable), 9.67 (brs, ½H, NH, D₂O exchangeable), 9.13 (brs, ½H, NH, D₂O exchangeable), 8.31 (s, 1H, OH, D₂O exchangeable), 7.82 (brs, ½H, NH, D₂O exchangeable), 7.56 (brs, ½H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H, J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 5.00 (d, 1H, J=4.8 Hz, OH, D₂O exchangeable), 3.82 (m, 1H, CH), 3.24 (m, 1H, CH), 3.12 (m, 1H, CH), 1.11 (d, 3H, J=6.0 Hz, CH₃).

3-Hydroxy-N-(trans-2-hydroxy-cyclohexyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 424; ¹H NMR(DMSO-d6): 10.61 (brs, ½H, NH, D₂O exchangeable), 9.74 (brs, ½H, NH, D₂O exchangeable), 9.60 (brs, ½H, NH, D₂O exchangeable), 9.08 (brs, ½H, NH, D₂O exchangeable), 8.34 (s, 1H, OH, D₂O exchangeable), 7.74 (brs, ½H, NH, D₂O exchangeable), 7.48 (brs, ½H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H, J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 5.08 (d, 1H, J=4.8 Hz, OH, D₂O exchangeable), 3.34 (m, 2H, 2×CH), 1.88 (m, 2H, CH₂), 1.63 (m, 2H, CH₂), 1.27 (m, 4H, 2×CH₂).

3-Hydroxy-N-[(S)-1-hydroxymethyl-3-methyl-butyl]-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 426; ¹H NMR(DMSO-d6): 10.49 (brs, ½H, NH, D₂O exchangeable), 9.81 (brs, ½H, NH, D₂O exchangeable), 9.50 (brs, ½H, NH, D₂O exchangeable), 9.15 (brs, ½H, NH, D₂O exchangeable), 8.34 (s, 1H, OH, D₂O exchangeable), 7.85 (brs, ½H, NH, D₂O exchangeable), 7.57 (brs, ½H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H, J=7.5 Hz, ArH), 6.94 (m, 6H, ArH), 4.99 (t, 1H, J=4.8 Hz, OH, D₂O exchangeable), 3.76 (m, 1H, CHN), 3.45 (m, 1H, CH₂O), 3.40 (m, 1H, CH₂O), 1.64 (m, 1H, CHMe₂), 1.41 (t, 2H, CH₂), 0.90 (d, 3H, J=6.6 Hz, CH₃), 0.87 (d, 3H, J=6.6 Hz, CH₃).

3-Hydroxy-N-[2-hydroxy-2-(3-hydroxy-phenyl)-ethyl]-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 462; ¹H NMR(DMSO-d6): 10.65 (brs, ½H, NH, D₂O exchangeable), 9.76 (brs, ½H, NH, D₂O exchangeable), 9.37 (brs, ½H, NH, D₂O exchangeable), 9.14 (brs, ½H, NH, D₂O exchangeable), 8.31 (s, 1H, OH, D₂O exchangeable), 7.84 (brs, ½H, NH, D₂O exchangeable), 7.57 (brs, ½H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (m, 2H, J=7.5 Hz, ArH), 6.94 (m, 6H, ArH), 6.85 (m, 2H, ArH), 6.64 (d, 1H, J=7.5 Hz, ArH), 5.76 (brs, 1H, OH, D₂O exchangeable), 4.69 (brs, 1H, OH, D₂O exchangeable), 4.12 (m, 1H, CH), 3.15 (d, 2H, J=4.2 Hz, CH₂).

Similar procedures can be used in the synthesis of N-2-(2-tetrahydrofuryl)ethyl-3-hydroxy-5-[4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylamino]-isothiazole-4-carboxamidine and N-2-(4-methylpiperazinyl)ethyl-3-hydroxy-5-[4-(2,5-dichloro-phenoxy)-3-fluoro-phenylamino]-isothiazole-4-carboxamidine, as shown below.

The scheme below shows alternative syntheses for compounds of this invention in which R′ includes a cyclic moiety.

The following synthetic procedure is provided as an example of synthesis scheme for compounds of formula VII.

4-Isothiocyanato-benzoic acid t-butyl ester 2: To 4-amino-t-butyl-benzoate 1, (25.0 g., 129.4 mmol) in a stirred biphasic mixture of CHCl₃ (250 ml) and saturated NaHCO₃ solution (100 ml) in an ice bath, thiophosgene (9.9 ml, 129.4 mmol) was added dropwise. After addition of thiophosgene stirring at room temperature was continued for 90 min. The organic layer was washed with water, dried over anhydrous Na₂SO₄, and further purified by column chromatography to provide 28.3 g. of 4-isothiocyanato-benzoic acid, t-butyl ester 2.

4-(2-carbamoyl-2-cyano-thioacetylamino)-benzoic acid t-butyl ester 3: To 28.3 g., 120.4 mmol of 4-isothiocyanato-benzoic acid t-butyl ester 2 in DMF (200 ml), KOH (6.74 g., 120.4 mmol) and cyanoacetamide (10.21 g., 120.4 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours, then acidified with 1N HCl. The precipitate obtained was filtered, washed with water, and dried under vacuum, to provide 32.10 g. of 4-(2-carbamoyl-2-cyano-thioacetylamino)-benzoic acid t-butyl ester 3.

4-(4-Cyano-3-hydroxy-isothiazole)-benzoic acid 4: To 4-(2-carbamoyl-2-cyano-thioacetylamino)-benzoic acid t-butyl ester 3 (32.10 gm, 100.36 mmol) in EtOAc (250 ml), Br₂ (5.2 ml, 100.36 mmol) was added slowly. The reaction mixture was kept stirring at room temperature for 2 hrs. The precipitate obtained was filtered and washed with saturated NaHCO₃ solution and dried under vacuum to provide 31 g. of 4-(4-cyano-3-hydroxy-isothiazole)-benzoic acid 4.

5-[4-(2,3-dihydro-indole-1-carbonyl)-phenylamino]-3-hydroxy-isothiazole-4-carbonitrile 5: To 1.0 g. 4-(4-cyano-3-hydroxy-isothiazole)-benzoic acid 4 (3.82 mmol) in DMF (30 ml) were added DMAP (dimethylaminopyridine)(0.46 gm, 3.82 mmol), EDC (1-ethyl-3,3′-dimethylaminopropyl carbodiimide HCl) (0.732 gm, 3.82 mmol) and indoline (1.28 gm, 3.82 mmol). The reaction mixture was kept stirring at room temperature for 16 h, concentrated to dryness, and purified by column chromatography to provide 1.08 gm of 5-[4-(2,3-Dihydro-indole-1-carbonyl)-phenylamino]-3-hydroxy-isothiazole-4-carbonitrile 5.

5-[4-(2,3-dihydro-indole-3-carbonyl)-phenylamino]-3-hydroxy-N-(2-hydroxy-1-methyl-ethyl)-isothiazole-4-carboxamidine 6: To 5-[4-(2,3-dihydro-indole-1-carbonyl)-phenylamino]-3-hydroxy-isothiazole-4-carbonitrile 5 (0.362 gm, 1 mmol) in 10 ml anhydrous EtOH was added (2-amino-propan-1-ol (0.375 gm, 5 mmol). The reaction mixture was maintained at 80° C. for 16 h. with stirring, then concentrated to dryness and purified by column chromatography to provide 5-[4-(2,3-dihydro-indole-1-carbonyl)-phenylamino]-3-hydroxy-N-(2-hydroxy-1-methyl-ethyl)-isothiazole-4-carboxamidine 6.

A typical synthetic scheme for compounds of formula VIII is shown below.

Compounds of formulas IX and X are prepared by standard synthetic procedures that are analogous with those employed for compounds of formulas II-VIII. A typical synthesis scheme for compounds of formula XI is illustrated by the procedure for a 5-(meta-indolecarbonylaryl amino isothizole amidine):

Synthesis scheme for a 5-(meta-dihydroindolecarbonylaryl amino isothiazole amidine):

Example: 5-[4-(2,3-dihydro-indole-1-carbonyl)-phenylamino]-3-hydroxy-N-(2-hydroxy-1-methyl-ethyl)-isothiazole-4-carboxamidine 6.

4-isothiocyanato-benzoic acid t-butyl ester 2: t-Butyl-4-aminobenzoate 1, (25.0 gm, 129.4 mmol) was taken into CHCl₃ (250 ml) and saturated NaHCO₃ (100 ml) in ice bath. To the stirred mixture thiophosgene (9.9 ml, 129.4 mmol) was added dropwise, and stirring continued for another 90 min. at room temperature after addition was complete. The organic layer was washed with water, dried over Na₂SO₄, and further purified by column chromatography to provide 28.3 gm of 4-isothiocyanato-benzoic acid t-butyl ester 2.

4-(2-carbamoyl-2-cyano-thioacetylamino)-benzoic acid t-butyl ester 3: 4-Isothiocyanato-benzoic acid t-butyl ester 2 (28.3 gm, 120.4 mmol) was taken into DMF (200 ml). To this KOH (6.74 gm, 120.4 mmol) and cyanoacetamide (10.21 gm, 120.4 mmol) were added. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was acidified with 1N HCl, the precipitate obtained was filtered, washed with water, and dried under vacuum, to provide 32.10 gm of 4-(2-Carbamoyl-2-cyano-thioacetylamino)-benzoic acid t-butyl ester 3.

4-(4-cyano-3-hydroxy-isothiazole)-benzoic acid 4: 4-(2-carbamoyl-2-cyano-thioacetylamino)-benzoic acid t-butyl ester 3 (32.10 gm, 100.36 mmol) was taken into EtOAc (250 ml) and to this Br₂ (5.2 ml, 100.36 mmol) was added slowly. Reaction mixture was stirred at room temperature for 2 h. The precipitate obtained was filtered and washed with saturated NaHCO₃ and dried under vacuum to provide 31 gm of 4-(4-cyano-3-hydroxy-isothiazole)-benzoic acid 4.

5-[3-(3-(1H-indole-1-carbonyl)phenylamino]-3-hydroxyisothiazole-4-carbonitrile 5: 4-(4-cyano-3-hydroxy-isothiazole)-benzoic acid 4 (1.0 gm, 3.82 mmol) was taken into DMF (30 ml). To this solution DMAP (0.46 gm, 3.82 mmol), EDC (0.732 gm, 3.82 mmol) and indoline (1.28 gm, 3.82 mmol) were added. The reaction mixture was stirred at room temperature for 16 h., concentrated to dryness, and purified by column chromatography to provide 1.08 gm of 5-[4-(2,3-dihydro-indole-1-carbonyl)-phenylamino]-3-hydroxy-isothiazole-4-carbonitrile 5.

5-[3-(3-(1H-indole-1-carbonyl)phenylamino]-3-hydroxy-N-(1-hydroxypropan-2-yl)isothiazole-4-carboximidamide 6: 5-[3-(3-(1H-indole-1-carbonyl)phenylamino)-3-hydroxyisothaizole-4-carbonitrile 5: (0.362 gm, 1 mmol) was taken into anhydrous EtOH (10 ml) and to this 2-amino-propan-1-ol (0.375 gm, 5 mmol) was added. The reaction mixture was stirred at 80° C. for 16 h., then concentrated to dryness and purified by column chromatography to provide 5-[4-(2,3-dihydro-indole-1-carbonyl)-phenylamino]-3-hydroxy-N-(2-hydroxy-1-methyl-ethyl)-isothiazole-4-carboxamidine 6.

Biological Data

Selected compounds were used in various assays to evaluate inhibitory activity of the compounds according to the inventive subject matter, and experimental procedures and results are indicated in tables below, where, unless otherwise indicated, “A” denotes inhibitory concentrations of 1 nM-100 nM, “B” denotes inhibitory concentrations of 100 nM-500 nM, and “C” denotes inhibitory concentrations of greater than 500 nM (hydroxy groups in the structures of the table below are denoted as single bonded oxygen as the structures were generated in “hide proton view”).

Generation of IC50 Data

Materials and preparation of reagents: Human GST-MEK1 and the constitutively active allele GST-MEK1^(CA) (harboring the mutations Ser218Asp and Ser222Asp) were subcloned into the yeast expression vector pGEM4Z (Promega, Madison, Wis.) from the wild type human MEK1 cDNA. GST-MEK1^(CA) was expressed in Escherichia coli and partially purified using Glutathione Sepharose 4B affinity resin (Amersham Pharmacia Biotech, Piscataway, N.J.). The ERK2 allele was subcloned from MAPK2/Erk2 cDNA (wild type) in pUSEamp (Upstate Biotechnology, Inc., Waltham, Mass.) into the vector pET21a (Novagen, Madison, Wis.) resulting in an N-terminal histidine-tagged mouse ERK2 allele. ERK2 was expressed and purified to homogeneity [Zhang, 1993 #33]. Myelin basic protein (MBP) was purchased from Gibco BRL (Rockville, Md.). EasyTides adenosine 5′-triphosphate (ATP) ([γ-³³P]) (NEN Perkin Elmer, Wellesley, Mass.) was the source of radiolabel for all kinase reactions. Activated Raf-1 (truncated) and activated MAPKinase 2/ERK2 were purchased from Upstate, Inc. (Lake Placid, N.Y.). 4-20% Criterion Precast gels were purchased from Bio-Rad (Hercules, Calif.).

Determination of enzymatic activity: Compounds were diluted from dimethylsulfoxide (DMSO) stocks into 1×HMNDE (20 mM HEPES pH 7.2, 1 mM MgCl₂, 100 mM NaCl, 1.25 mM DTT, 0.2 mM EDTA). A typical 25-microliter assay contained 0.002 nanomoles MEK1^(CA), 0.02 nanomoles ERK2, 0.25 nanomoles MBP, 0.25 nanomoles unlabeled ATP, and 0.1 μCi [γ³³P] ATP. The screening assay essentially comprised four additions. Five μl of diluted compound were dispensed to 96-well assay plates. Ten μl of 2.5× enzyme cocktail (MEK1^(CA) and ERK2 only) were then added to each well followed by a pre-incubation for 30 minutes at ambient temperature. Ten μl of 2.5× substrate cocktail (labeled and unlabeled ATP plus MBP) were then added, followed by incubation for 60 minutes at ambient temperature. Finally, 100 μl of 10% trichloroacetic acid (TCA) were added and incubated for 30 minutes at room temperature to halt the reaction and precipitate radiolabeled protein products. Reaction products were harvested on glass fiber 96 well filter plates prewetted with water and 1% pyrophosphate. The filter plate was then washed 5 times with water. Water was displaced by absolute ethanol and the plate was allowed to air dry for 30 minutes at room temperature. A back seal was applied manually and 40 μl of scintillation cocktail were dispensed to each well. A top seal was applied and the plate was counted in the TopCount for two seconds per well.

Generation of EC50 Data

Effects of compounds in the cell were determined by Western blotting for phosphorylated ERK. MDA-MB-231 breast cancer cells were plated in a 48 well plate at 20,000 cells per well and grown in a 37° humidified CO₂ incubator. The following day, the growth media (DMEM+10% fetal bovine serum) was removed and replaced with starve media (DMEM+0.1% fetal bovine serum). Cells were incubated in the starve media for sixteen hours and then treated with a range of compound concentrations for thirty minutes. After incubation with compound, cells were stimulated with 100 ng/ml EGF for five minutes. The cells were then lysed and analyzed by Western blot using a monoclonal antibody raised to phosphorylated ERK. The signal was amplified using a secondary antibody conjugated to a near −IR dye and detected on a Licor Odyssey scanner. The intensity of signal was quantitated and this data was used to generate dose response curves and EC50 calculations. TABLE 1 Biological Activity of Compounds of Formula I # Structure Avg IC50 1

B 2

B 3

C 4

B 5

B 6

A 7

B 8

C 9

A 10

A 11

A 12

A 13

A 14

B 15

A 16

A 17

B 18

B 19

A 20

B 21

A 22

A 23

A 24

C 25

A 26

C 27

B 28

A 29

B 30

B 31

A 32

A 33

A 34

B 35

B 36

B 37

A 38

B 39

A 40

A 41

B 42

A 43

A 44

C 45

A 46

A 47

A 48

A 49

A 50

A 51

A 52

A 53

B 54

B 55

B 56

C 57

C 58

C 59

C 60

C 61

B 62

C 63

B 64

C 65

B 66

C 67

C 68

C 69

C 70

B 71

C 72

C 73

B 74

C 75

B 76

C 77

A 78

C 79

B 80

C 81

C 82

B 83

B 84

B 85

B 86

B 87

C 88

C 89

C 90

C 91

C 92

C 93

C 94

B 95

C 96

C 97

C 98

C 99

C 100

A 101

B 102

B 103

B 104

B 105

C 106

C 107

C 108

C 109

A 110

B 111

C 112

C 113

C 114

C 115

C 116

C 117

C 118

C 119

C 120

C 121

C 122

C 123

C 124

B 125

C 126

C 127

B 128

B 129

B 130

A 131

C 132

C 133

C 134

C 135

C 136

C 137

C 138

B 139

B 140

A 141

B 142

A 143

A 144

A 145

C 146

C 147

B 148

C 149

C 150

C 151

C 152

A 153

B 154

A 155

B 156

B 157

B 158

B 159

A 160

B 161

C 162

C 163

B 164

A 165

B 166

A 167

B 168

C 169

B 170

B 171

C 172

C 173

A 174

A 175

A 176

B 177

B 178

A 179

B 180

B 181

C 182

B 183

A 184

C 185

B 186

C 187

C 188

B 189

B 190

B 191

B 192

B 193

C 194

C 195

C 196

C 197

B 198

A 199

A 200

A 201

B 202

A 203

C 204

C 205

B 206

C 207

C 208

C 209

B 210

B 211

C 212

B 213

A 214

C 215

C 216

C 217

C 218

A “A” denotes inhibitory concentrations of 1 nM-100 nM, “B” denotes inhibitory concentrations of 100 nM-500 nM, and “C” denotes inhibitory concentrations of greater than 500 nM.

TABLE 2 Biological Activity of Compounds of Formula I, where Ar¹-A contains an amido or indolo group # Structure Avg IC50 219

A 220

C 221

B 222

A 223

A 224

B 225

A 226

A 227

C 228

A 229

A 230

C 231

B 232

A 233

B 234

B 235

A 236

A 237

A 238

A 239

A 240

B 241

B 242

B 243

B 244

C 245

C 246

A 247

B 248

A 249

A 250

A 251

A 252

A 253

C 254

B 255

A 256

A 257

C 258

C 259

C 260

B 261

A 262

C 263

A 264

C 265

C 266

C 267

A 268

B 269

A 270

C 271

C 272

A 273

A 274

A 275

A 276

C 277

A 278

A 279

A 280

A 281

B 282

C 283

A 284

B 285

C 286

A 287

A 288

A 289

A 290

A 291

A 292

A 293

A 294

B 295

A 296

B 297

B 298

B 299

C 300

A 301

A 302

B 303

A 304

A 305

A 306

A 307

A 308

B 309

C 310

A 311

B 312

A 313

C 314

C 315

C 316

A 317

B 318

B 319

A 320

A 321

A 322

A 323

B 324

B 325

C 326

A 327

A 328

A 329

A 330

A 331

A 332

B 333

A 334

A 335

A 336

C 337

A 338

A 339

A 340

A 341

A 342

A 343

C 344

C 345

A 346

A 347

A 348

A 349

A 350

A 351

B 352

A 353

A 354

A 355

A 356

A 357

A 358

B 359

B 360

A 361

B 362

A 363

C 364

A 365

B 366

A 367

A 368

A 369

A 370

A 371

B 372

B 373

A 374

A 375

A 376

A 377

C 378

B 379

B 380

B 381

A 382

A 383

A 384

B 385

A 386

C 387

B 388

B 389

C 390

B 391

B 392

B 393

A 394

A 395

B 396

B 397

C 398

B 399

B 400

B 401

A 402

A 403

B 404

A 405

A 406

A 407

A 408

A 409

A 410

A 411

B 412

A 413

B 414

A 415

A 416

B 417

C 418

B 419

C 420

C 421

A 422

A 423

A 424

A 425

B 426

A 427

C 428

B 429

B 430

B 431

A 432

B 433

A 434

A 435

A 436

B 437

A 438

A 439

C 440

A 441

A 442

A 443

A 444

A 445

A 446

A 447

A 448

A 449

A 450

A 451

A 452

A 453

A 454

A 455

A 456

B 457

A 458

A 459

A 460

A 461

A 462

B 463

A 464

A 465

B 466

A 467

A 468

A 469

A 470

A 471

C 472

A 473

A 474

A 475

A 476

A 477

A 478

A 479

C 480

A 481

A 482

A 483

A 484

A 485

B 486

C 487

A 488

C 489

C 490

B 491

C 492

B 493

A 494

A 495

C 496

C 497

A 498

B 499

B 500

A 501

B 502

A 503

B 504

B 505

A 506

B 507

C 508

C 509

C 510

C 511

C 512

C

A″ denotes inhibitory concentrations of 1 mM-200 nM, “B” denotes inhibitory concentrations of 200 nM-1000 nM, and “C” denotes inhibitory concentrations of greater than 100 nM.

Examples of compounds of the present invention are provided in the following table. TABLE 3 COMPOUND IC 50 E-1

C E-2

C E-4

C E-5

C E-6

C E-7

C E-8

B E-9

B E-10

A E-11

A E-12

B E-13

C E-14

C E-15

C E-16

A E-17

C E-18

C E-19

C E-20

A E-21

B E-22

C

Biological Activity of Compounds of Formula X—Activity of Benzamides

In the following table IC50's of several benzamides are compared. Here, “A” denotes inhibitory concentrations of 1 nM-100 nM, “B” denotes inhibitory concentrations of 100 nM-500 nM, and “C” denotes inhibitory concentrations of greater than 500 nM. TABLE 4 COMPOUND IC 50

B

A

C

A

Biological Activity of Compounds of Formula I, where R′ is (CH₂)_(1 or 2)-G, where G is a Five- or Six-Membered Ring or a 9- to 14-Member Fused Ring System

The following table shows the effects of substitution in R′. “A” denotes inhibitory concentrations of 1 nM-100 nM, “B” denotes inhibitory concentrations of 100 nM-500 nM, and “C” denotes inhibitory concentrations of greater than 500 nM. Compound IC50 EC50

A A

A A

A A

B B

B B

A B

A A

A A

B B

B

A

B

C

A

C

B

A

B

B 

1. A compound of formula I

where Ar¹ is phenyl, pyridyl, pyrimidyl, pyridazinyl, or triazinyl, in which all ring carbon atoms are optionally substituted with substituents R₁, R₂, and R₃, which are selected independently from hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂; and R₁ may also be 2-C(O)K, where K is selected from: OJ, where J is isopropyl, cyclopropyl, cyclopentyl, dimethylamino, or methoxyethyl; NHJ′ where J′ is methyl, ethyl, isopropyl, cyclopropyl, dimethylaminomethyl, or 3-methyl-2-yl-butanoic acid methyl ester: and N(CH₃)₂; or 4-methylpiperzin-1-yl; or R₁ and R₂ are attached to adjacent carbons and, together with the ring atoms to which they are attached, form an additional, fused, five- or six-membered ring, optionally containing one heteroatom, which ring may be aromatic or aliphatic; A is O, S, CH₂, N₂, CO, NHCO, COCH₂, or CH₂CO; or Ar¹-A is

where the five-membered ring is fused to Ar¹ and Y is NH, S, or O; or Ar¹-A is

where the dotted line represents an optional double bond, the five-membered ring is fused to Ar¹, and R_(x) is selected from substituents listed above for R₃; or Ar¹-A is

where the five-membered ring is fused to Ar¹, and R_(x) is selected from substituents listed above for R₃; Ar² is phenyl, pyridyl, pyrimidyl, pyridazinyl, or triazinyl, where ring carbon atoms are optionally substituted with substituents R₄-R₆ which are selected independently from H, F, Cl, Br, CH₃, or CF₃; or Ar²—NH— is

where R_(y) is selected from substituents listed above for R₃; and R′ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups are optionally substituted with one to three groups selected independently from hydroxy, halogen, and methyl; or R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is a five- or six-membered ring or a 9-14-membered fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds; or R′ is —CH(CH₂OH)CH₂D, where D is selected from imidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, and adamantin-1-yl.
 2. The compound of claim 1 shown in formula II

where substituents R₁-R₆ and R′ are as defined for formula I and R* is H, except when R₁ and R₂ are both F, and when R₁ and R₂ are both F, R* is either H or Cl.
 3. The compound of claim 2 shown in formula III

wherein A is —O—, —CH₂—, —N₂—, —CH₂C(O)—, —S—, or —C(O)—; R₁, R₂, and R₃ are, independently, hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂; or R₁ and R₂ are attached to adjacent carbons and, together with the ring atoms to which they are attached, form an additional, fused, five- or six-membered ring, optionally containing one heteroatom, which ring may be aromatic or aliphatic; R₄-R₆ are, independently, H, F, Cl, Br, CH₃, or CF₃; R* is H, except when R₁ and R₂ are both F; when R₁ and R₂ are both F, R* is either H or Cl; R′ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups are optionally substituted with one to three groups selected independently from hydroxy, halogen, and methyl; or R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is a five- or six-membered ring or a 9-14-membered fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds.
 4. The compound of claim 1 shown in formula IV

wherein U, V, W, X, Y, and Z are, independently CH or N, provided that U, V, W, X, Y, and Z are not all CH; A is —O—, —CH₂—, —N₂—, —NHC(O)—, —S—, or —C(O)—; R₁ and R₂ are, independently, hydrogen; halogen; hydroxy; cyano; CH₃, optionally substituted with 1-3 fluorine atoms; CH₃O; (CH₃)₂N; CH₃OC(O); 2-methoxy ethenyl; and CH₃CH₂OC(O); and R′ is OH; OC₁-C₆ alkyl; C₁-C₆ alkyl, optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups are optionally substituted with one to three groups selected independently from hydroxy, halogen, and methyl.
 5. The compound of claim 4 shown in formula V

wherein Q₁ and Q₂ are, independently CH or N, provided that Q₁ and Q₂ are not both CH; R₁ and R₂ are, independently, hydrogen; halogen; hydroxy; cyano; CH₃, optionally substituted with 1-3 fluorine atoms; CH₃O; (CH₃)₂N; CH₃OC(O); 2-methoxy ethenyl; and CH₃CH₂OC(O); and R′ is selected from C₁-C₆ alkyl, optionally substituted with 1-3 hydroxyl groups; cyclopropyl; —CH₂B; and —CH₂CH₂B, where B is selected from C₃₋₆ cycloalkyl, phenyl, pyridyl, piperzin-1-yl, piperidin-1-yl, N-morpholyl, tetrahydrofuryl, and naphthyl.
 6. The compound of claim 1 shown in formula VI

where Y is —NH—, —S— or —O—, and R′ is selected from I-hydroxy-isopropyl, 2-hydroxy-n-propyl, 2-hydroxy-ethyl, and 2,3,-dihydroxy-n-propyl.
 7. The compound of claim 1 shown in Formula VII

where the dashed bond represents an optional double bond, and where symbols T-Z represent N, CH, or CR_(1, 2, or 4), provided that at most two of W, X, Y, and Z and at most 2 of T, U, and V are N; where R₁-R₄ are, independently, hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₆ alkyl; O—C₁-C₆ alkyl; C₂-C₆ alkenyl; C₂-C₆ alkynyl; C₁-C₆ cycloalkyl; 2-methoxy ethenyl; CH₃OC(O); CH₃CH₂OC(O); C₁-C₅ alkyl-C(O)—; C₁-C₅ alkyl-C(O)O—; —NR₆R₇, —CH₂NR₆R₇, —NH—C(O)—R₆, —C(O)NR₈R₉; CH₃S(O)₂—, or —S(O)₂NR₈R₉, where R₆-R₉ are, independently, H or C₁-C₄ alkyl; or any of the pairs R₁ and R₂, R₆ and R₇, or R₈ and R₉ are attached to adjacent carbons and, together with the ring atoms to which they are attached, form an additional, fused, five- or six-membered ring, optionally containing one or two heteroatoms selected from O, N, and S, which ring may be aromatic or aliphatic; wherein all alkyl, alkenyl, and cycloalkyl groups and all rings are optionally substituted with 1-3 halogen atoms, and all rings are also optionally substituted with 1-3 C₁-C₃ alkyl groups or trifluoromethyl groups; R₅ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; or R₅ is —(CH₂)_(n)—B where n is 1 or 2 and B is a five- or six-membered ring or a 9- to 14-member fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds.
 8. The compound of claim 1 shown in Formula VIII below, where the dashed bond represents an optional double bond,

where R₁-R₄ are, independently, hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₆ alkyl; O—C₁-C₆ alkyl; C₂-C₆ alkenyl; C₂-C₆ alkynyl; C₁-C₆ cycloalkyl; 2-methoxy ethenyl; CH₃OC(O); CH₃CH₂OC(O); C₁-C₅ alkyl-C(O)—; C₁-C₅ alkyl-C(O)O—; —NR₆R₇—CH₂NR₆R₇, —NH—C(O)—R₆, —C(O)NR₈R₉; CH₃S(O)₂—, or —S(O)₂NR₈R₉, where R₆-R₉ are, independently, H or C₁-C₄ alkyl; or any of the pairs R₁ and R₂, R₆ and R₇, or R₈ and R₉ are attached to adjacent carbons and, together with the ring atoms to which they are attached, form an additional, fused, five- or six-membered ring, optionally containing one or two heteroatoms selected from O, N, and S, which ring may be aromatic or aliphatic; wherein all alkyl, alkenyl, and cycloalkyl groups and all rings are optionally substituted with 1-3 halogen atoms; R₅ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; or R₅ is —(CH₂)_(n)—B where n is 1 or 2 and B is a five- or six-membered ring or a 9- to 14-member fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds.
 9. The compound of claim I shown in formula IX, where the dashed bond represents an optional double bond, where R₁-R₅ are defined as for formula A, and where symbols W-Z represent N, CH, or CR_(1 or 2), provided that at least one of W-Z is N.


10. The compound of claim 1 shown in formula X

where M, Q, T, U, and V represent N, CH, or CR_(1, 2, or 3), provided that no two nitrogen atoms are adjacent, where R₁-R₄ are, independently, hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₆ alkyl; O—C₁-C₆ alkyl; C₂-C₆ alkenyl; C₂-C₆ alkynyl; C₁-C₆ cycloalkyl; 2-methoxy ethenyl; CH₃OC(O); CH₃CH₂OC(O); C₁-C₅ alkyl-C(O)—; C₁-C₅ alkyl-C(O)O—; —NR(R₇, —CH₂NR₆R₇, —NH—C(O)—R₆, —C(O)NR₈R₉; CH₃S(O)₂—, or —S(O)₂NR₈R₉, where R₆-R₉ are, independently, H or C₁-C₄ alkyl; or any of the pairs R₁ and R₂, R₆ and R₇, or R₈ and R₉, together with the ring atoms to which they are attached, form an additional, five- or six-membered ring, optionally containing one or two heteroatoms selected from O, N, and S, which ring may be aromatic or aliphatic, and which ring is fused in the case of R₁ and R₂; and where R₁ may also be isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, tolyl, or phenyl, wherein all alkyl, alkenyl, and cycloalkyl groups and all rings are optionally substituted with 1-3 halogen atoms, C₁-C₃ alkyl groups, or trifluoromethyl groups; R₅ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; or R₅ is —(CH₂)_(n)-G where n is 1 or 2 and G is a five- or six-membered ring or a 9- to 14-member fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds.
 11. The compound of claim 1 shown in formula XI

where M, Q, T, U, V, W, X, Y, and Z represent N, CH, or CR_(1, 2, 3, or 4), where R₁-R₄ are, independently, hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₆ alkyl; O—C₁-C₆ alkyl; C₂-C₆ alkenyl; C₂-C₆ alkynyl; C₁-C₆ cycloalkyl; 2-methoxy ethenyl; CH₃OC(O); CH₃CH₂OC(O); C₁-C₅ alkyl-C(O)—; C₁-C₅ alkyl-C(O)O—; —NR₇, —CH₂NR₆R₇, —NH—C(O)—R₆, —C(O)NR₈R₉; CH₃S(O)₂—, or —S(O)₂NR₈R₉, where R₆-R₉ are, independently, H or C₁-C₄ alkyl; or any of the pairs R₁ and R₂; R₆ and R₇, or R₈ and R₉ are attached to adjacent carbons and, together with the ring atoms to which they are attached, form an additional, fused, five- or six-membered ring, optionally containing one or two heteroatoms selected from O, N, and S, which ring may be aromatic or aliphatic; and where R₁ may also be isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, tolyl, or phenyl, wherein all alkyl, alkenyl, and cycloalkyl groups and all rings are optionally substituted with 1-3 halogen atoms, C₁-C₃ alkyl groups, or trifluoromethyl groups; R₅ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; or R₅ is —(CH₂)_(n)-G where n is 1 or 2 and G is a five- or six-membered ring or a 9- to 14-member fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds.
 12. The compound of claim 11, where M, Q, T, U, V, W, X, Y, and Z are all CH or CR_(1, 2, 3, or 4).
 13. The compound of claim 1 shown in formula XII

where the dashed bond represents an optional double bond, and where symbols L, T, U, V, and W-Z represent N, CH, or CR_(1, 2, or 4), provided that no two nitrogen atoms are adjacent, where R₁-R₄ are, independently, hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₆ alkyl; O—C₁-C₆ alkyl; C₂-C₆ alkenyl; C₂-C₆ alkynyl; C₁-C₆ cycloalkyl; 2-methoxy ethenyl; CH₃OC(O); CH₃CH₂OC(O); C₁-C₅ alkyl-C(O)—; C₁-C₅ alkyl-C(O)O—; —NR₆R₇—CH₂NR₆R₇—NH—C(O)—R₆, —C(O)NR₈R₉; CH₃S(O)₂—, or —S(O)₂NR₈R₉, where R₆-R₉ are, independently, H or C₁-C₄ alkyl; or any of the pairs R₁ and R₂, R₆ and R₇, or R₈ and R₉, together with the ring atoms to which they are attached, form an additional, five- or six-membered ring, optionally containing one or two heteroatoms selected from O, N, and S, which ring may be aromatic or aliphatic, and which ring is fused in the case of R₁ and R₂; and where R₁ may also be isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, tolyl, or phenyl, wherein all alkyl, alkenyl, and cycloalkyl groups and all rings are optionally substituted with 1-3 halogen atoms, C₁-C₃ alkyl groups, or trifluoromethyl groups; R₅ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionally substituted with one to three groups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; or R₅ is —(CH₂)_(n)-G, where n is 1 or 2 and G is a five- or six-membered ring or a 9- to 14-member fused ring system, wherein each ring optionally contains 1-3 heteroatoms selected independently from O, N, and S; wherein each ring is optionally substituted with 1-3 groups selected independently from the following: halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substituted with one to three halogen atoms; and wherein each ring optionally contains one or more double bonds. 